| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.54552002 |
| The structure activity data provide a unique view of the interactions between Shh and Ptc that is not readily attainable by conventional mapping strategies . . 0.54552002^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Ihh has biological properties similar to those of Sonic hedgehog ( Shh ) , including the ability to regulate the conserved targets Patched ( Ptc ) and Gli . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| PTC , a vertebrate homolog of this Drosophila gene , is genetically downstream of Sonic hedgehog ( Shh ) in the limb bud . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We show that Ptc can form a physical complex with a newly cloned vertebrate homologue of the Drosophila protein Smoothened ( vSmo ) , and that vSmo is coexpressed with vPtc in many tissues but does not bind Shh directly . ^^^ These findings , combined with available genetic evidence from Drosophila , support the hypothesis that Ptc is a receptor for Shh , and that vSmo could be a signalling component that is linked to Ptc . . ^^^ Here we describe binding studies using labelled Shh that strongly suggest that the Hh receptor is encoded by patched ( ptc ) , a gene first identified in genetic screens in Drosophila . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Beginning around 16 . 5 dpc , when Shh and Ptc RNA levels are normally both declining , this treatment caused an increase in the ratio of interstitial mesenchyme to epithelial tubules in transgenic compared to normal lungs . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Gene regulatory relationships defined in the fruit fly Drosophila suggest that overproduction of Sonic hedgehog ( SHH ) , the ligand for PTC , will mimic loss of ptc function . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We also show that Gli is expressed ectopically along with Ptc and Shh in Strong ' s luxoid mutant mice . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The transcript of Ptc , the putative receptor for Shh protein , can be detected anteriorly as well . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| In Drosophila , HH acts by inactivating PTC function , raising the possibility that overexpression of Sonic Hedgehog ( SHH ) in human epidermis might have a tumorigenic effect equivalent to loss of PTC function . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Further , ectopic expression of Gli 1 in the dorsal midbrain and hindbrain of transgenic mice mimics the effects of ectopically expressed Shh N , leading to the activation of ventral neural tube markers such as Ptc , HNF 3beta , and Shh ; to the suppression of dorsal markers such as Pax 3 and AL 1 ; and to the formation of ectopic dorsal clusters of dopaminergic and serotonergic neurons . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The PATCHED ( PTC ) gene encodes a Sonic hedgehog ( Shh ) receptor and a tumor suppressor protein that is defective in basal cell nevus syndrome ( BCNS ) . ^^^ Two Shh target genes , ptc itself and Gli , were derepressed in the ectoderm and mesoderm but not in the endoderm . ^^^ Thus Ptc appears to be essential for repression of genes that are locally activated by Shh . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Expression of Gli and Gli 3 , but not of Gli 2 , is subsequently downregulated at the canalicular stage , coincident with a decline in the expression of sonic hedgehog ( Shh ) and the hedgehog receptor gene , patched ( Ptc ) . ^^^ Overexpression of Shh in the lung results in increased levels of Ptc mRNA . ^^^ Gli , but not Gli 2 , is also upregulated , suggesting a differential involvement of the Gli genes in the regulation of Ptc by SHH during lung development . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Familial BCCs and a fraction of sporadic BCCs have lost the function of Patched ( Ptc ) , a Sonic hedgehog ( Shh ) receptor that acts negatively on this signalling pathway . ^^^ Moreover , loss of Ptc or overexpression of Shh can not be the sole causes of Gli 1 induction and sporadic BCC formation , as they do not occur consistently . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The mutant gene product is sufficient to fulfil the signalling properties of Shh including upregulation of the direct Shh target genes Ptc and Gli , and induction of the downstream target genes Bmp 2 , Fgf 4 and Hoxd 13 . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Interestingly , Shh and Ptc started to be expressed in patched pattern along the osteogenic fronts at the end of embryonic development and , at this time , the expression of Bmp 4 and sequentially those of Msx 2 and Bmp 2 were reduced , and they also acquired patched expression patterns . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Within the cerebellum , Shh , Ptc , and Smo transcripts were colocalized in the Purkinje cell layer . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Here we show that the feather tract is initiated by a continuous stripe of Shh , Fgf 4 , and Ptc expression in the epithelium , which then segregates into discrete feather primordia that are more strongly Shh and Fgf 4 positive . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We report that the expression of known Shh responsive genes such as Ptc and Gli 1 is downregulated in mutant mice lacking Gli 2 function . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Virally mediated misexpression of Shh results in ectopic upregulation of its receptor Ptc and a cellular proliferation throughout the gut mesoderm . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The expression of genes involved in the Sonic Hedgehog signalling pathway , including Shh , Ptc , Smo , Gli 1 , Gli 2 and Gli 3 , were found to be expressed in temporal and spatial patterns during early murine tooth development , suggestive of a role in early tooth germ initiation and subsequent epithelial mesenchymal interactions . ^^^ Of these Ptc , Smo , Gli 1 , Gli 2 and Gli 3 were expressed in epithelium and mesenchyme whereas Shh was only detected in epithelium . ^^^ Ectopic application of Shh protein to mandibular mesenchyme induced the expression of Ptc and Gli 1 . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Whereas Shh and Wnt10b can induce general Hedgehog and Wnt targets , Ptc and Gli for Shh and Lef 1 for Wnt10b , only Bmp 2 is able to induce tooth specific expression of Msx 1 . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The distribution of mRNA for patched ( ptc ) , the membrane receptor for shh , was also indistinguishable between both groups . ^^^ These data show that maternal cocaine treatment during early neural tube development does not significantly alter the expression patterns of shh or ptc mRNA . ^^^ Thus , congenital defects and behavioral abnormalities associated with maternal cocaine use do not appear to result from altered expression of the shh ptc pathway . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Genetic and biochemical data suggest that the Sonic hedgehog ( Shh ) receptor is composed of at least two proteins : the tumor suppressor protein Patched ( Ptc ) and the seven transmembrane protein Smoothened ( Smo ) . ^^^ RESULTS : Using a biochemical assay for activation of the transcription factor Gli , a downstream component of the Hh pathway , we show here that Smo functions as the signaling component of the Shh receptor , and that this activity can be blocked by Ptc . ^^^ The inhibition of Smo by Ptc can be relieved by the addition of Shh . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Lingual expression of the signaling molecule Sonic hedgehog ( Shh ) , its receptor Patched ( Ptc ) , and the Shh activated transcription factor Gli 1 were assayed by using in situ hybridization . ^^^ Ptc and Gli 1 expression follow a pattern similar to that of Shh . ^^^ Compared with Shh , Ptc is expressed in larger regions surrounding the central papillary cells and also in the mesenchyme underlying Shh expressing epithelium . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Expression of ptc and gli genes in talpid 3 suggests bifurcation in Shh pathway . talpid 3 is an embryonic lethal chicken mutation in a molecularly un characterised autosomal gene . ^^^ Here we examine expression of patched ( ptc ) , which encodes a component of the Shh receptor , and is probably itself a direct target of Shh signalling , to establish whether talpid 3 acts in the Shh pathway . ^^^ We also describe genetic mapping of gli 1 , ptc , shh and smoothened in chickens and confirm by co segregation analysis that none of these genes correspond to talpid3 . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| PCs are thought to provide trophic support for granule neurons [ 2 ] [ 3 ] and to stimulate the proliferation of cells in the EGL [ 4 ] , but the signalling molecules that mediate these cell cell interactions have not been identified . 1 show here that PCs in the developing mouse cerebellum express the gene encoding the morphogen Sonic hedgehog ( Shh ) and that dividing cells in the EGL express Patched ( Ptc ) and Gli 1 , two target genes of which expression is upregulated in response to Hedgehog signalling ( see [ 5 ] and references therein ) . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Expression of BMP 7 , shh , and ptc were uneffected by RET Ig treatment , implying that these genes are regulated independently of ret . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We have used the mouse developing tooth germ as a model system to explore the transmission of Sonic hedgehog ( Shh ) signal in the induction of Patched ( Ptc ) . ^^^ In the early developing molar tooth germ , Shh is expressed in the dental epithelium , and the transcripts of Shh downstream target genes Ptc and Gli 1 are expressed in dental epithelium as well as adjacent mesenchymal tissue . ^^^ In wild type E11 . 0 molar tooth mesenchyme SHH soaked beads induced the expression of Ptc and Gli 1 . ^^^ However , in Msx 1 mutant dental mesenchyme SHH soaked beads were able to induce Gli 1 but failed to induce Ptc expression , indicating a requirement for Msx 1 in the induction of Ptc by SHH . ^^^ We conclude that in the context of the tooth germ Msx 1 is a component of the Shh signaling pathway that leads to Ptc induction . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The following findings suggest that Sonic hedgehog ( Shh ) is one of the signals . ( 1 ) RGCs express both Shh mRNA and protein , whereas the optic nerve contains the protein but not the mRNA . ( 2 ) Astrocytes and their precursors in the developing optic nerve express the Hedgehog ( Hh ) receptor gene Patched ( Ptc ) , suggesting that they are being signalled by an Hh protein . ( 3 ) Ptc expression in the nerve is greatly decreased by either nerve transection or by treatment with neutralizing anti Shh antibodies , suggesting that it depends on axon derived Shh . ( 4 ) Astrocyte proliferation in the developing nerve is reduced by treatment with anti Shh antibodies , suggesting that Shh normally helps stimulate this proliferation . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Overexpression of ptc 1 inhibits induction of Shh target genes and prevents normal patterning in the neural tube . ^^^ We find that excess Ptc is sufficient to inhibit expression of Gli 1 and ptc 1 , suggesting that Sonic hedgehog ( Shh ) can not signal effectively . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Ptc , Gli 1 , Bmp 2 , Hoxd 13 , and Fgf 4 are expressed throughout the anteroposterior axis of the mutant limb bud , despite normal Shh expression . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We favor the alternative , that Shh N functions primarily as a ligand for the putative receptor Patched ( Ptc ) . ^^^ This possibility is supported by new evidence for direct binding of Shh N to Ptc and by a strong correlation between the affinity of Ptc binding and the signaling potency of Shh N protein variants carrying alterations of conserved residues in a particular region of the protein surface . ^^^ These results together suggest that direct Shh N binding to Ptc is a critical event in transduction of the Shh N signal . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| In basal cell nevus syndrome ( BCNS ) patients , mutations of a gene , patched ( ptc ) , which encodes a putative signal transducer of sonic hedgehog protein ( SHH ) , were found and are thought to be one of the major causes of BCNS . ^^^ The SHH signaling pathway is an important developmental pathway , and ptc protein ( PTC ) is a suppressive component serving as a receptor for the secreted SHH . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Shh might exert its biological functions through binding to patched ( Ptc ) associated with smoothened ( Smo ) , leading to downstream activation of target genes such as the transcription factor Gli 1 . ^^^ We have performed a detailed localization of cells expressing transcripts of Shh , Ptc , Smo and Gli 1 in brain and spinal cord of the adult rat as well as in the developing cerebellum . ^^^ Ptc positive cells were frequently observed in brain areas devoid of any Shh transcripts , except in the median eminence or the facial nucleus , suggesting local Shh signalling . ^^^ The presence of Shh , Ptc and Smo transcripts in hypothalamic areas may indicate a role of Shh signalling in the modulation of neuroendocrine functions . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We show that the two putative receptors of the Shh ligand , Ptc and Ptch 2 , localise in different cells , suggesting Shh may function in different ways as an epithelial and mesenchymal signal . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Transcripts for the putative Shh receptor genes patched ( Ptc ) and smoothened ( Smo ) are expressed by embryonic , postnatal , and adult progenitor cells , suggesting that Shh can act directly on these cells . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The ontogeny of expression of the mesodermal markers shh , ptc , bmp 2 , and hoxd 12 and 13 , as well as the ectodermal markers wnt7a , fgf 4 , fgf 8 , cx 43 , and p 21 occurred normally in day 9 . 5 teratogen exposed limb buds . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We also explored time dependency and range of Shh signalling by examining ptc expression . ^^^ We show that high level ptc expression is induced rapidly when either Shh beads or polarising regions are grafted to a host limb . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Using samples from a population based birth defects registry in California , we performed a mutational analysis of the known HPE genes Sonic Hedgehog ( SHH ) , ZIC 2 , and SIX 3 , in addition to two HPE candidate genes , TG interacting factor ( TGIF ) , and Patched ( PTC ) , on a group of sporadic HPE patients . ^^^ No sequence changes were detected in SHH , ZIC 2 , and PTC . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Sonic hedgehog ( Shh ) and Patched ( Ptc ) expression appeared unaffected in the transgenic limb buds , suggesting that the BMPR IB mediated signaling pathway is downstream from Shh . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| By using a murine retrovirus to ectopically express Wnt 7b in presumptive dental ectoderm in mandibular arch explants , we show that Shh expression in the ectoderm and Ptc expression in the underlying ectomesenchyme are down regulated , and tooth development is subsequently arrested . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Defects in a developmental signaling pathway involving mammalian homologues of the Drosophila segment polarity gene , patched ( ptc ) and its ligand , sonic hedgehog ( shh ) , contribute to tumor formation in several tissues . ^^^ High levels of glil mRNA and protein were detected in the tumors , suggesting that the shh / ptc pathway was activated despite the persistence of ptc expression . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We have tested whether this activity of cyclopamine is related to disruption of cellular cholesterol transport and putative secondary effects on the Shh receptor , Patched ( Ptc ) . ^^^ However , compounds that block cholesterol transport by affecting the vesicular trafficking of the Niemann Pick C 1 protein ( NPC 1 ) , which is structurally similar to Ptc , are weak Shh antagonists . ^^^ Rather than supporting a direct link between cholesterol homeostasis and Shh signaling , our findings suggest that the functions of both NPC 1 and Ptc involve a common vesicular transport pathway . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Shh internalization is blocked by a monoclonal antibody whose epitope overlaps the Ptc binding site of Shh . ^^^ These findings suggest that Shh internalization is mediated by Ptc 1 and may be linked to signaling . ^^^ Concordantly , transfection of mammalian cell lines with a Ptc 1 cDNA confers the ability to internalize multiple forms of Shh , including transmembrane anchored Shh , by a dynamin dependent process . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The similarity of the Shh receptor , Patched ( Ptc ) , to the Niemann Pick Cl protein , which is involved in the vesicular trafficking of cholesterol , provides insight into the role of cholesterol and the action of compounds like cyclopamine . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We further demonstrate that the availability of s ShhNp is regulated by two functional antagonists of the Shh pathway , Patched ( Ptc ) and Hedgehog interacting protein ( Hip ) . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Shh and Ptc are associated with taste bud maintenance in the adult mouse . ^^^ We found that the receptor for Sonic hedgehog ( Shh ) , Patched 1 ( Ptc ) , was expressed around taste buds where cells were proliferating , and that Shh was expressed within basal cells of taste buds . ^^^ Denervation caused the loss of Shh and Ptc expression before the degeneration of taste buds . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Sonic Hedgehog ( Shh ) and Patched ( Ptc ) were found only in the dorsal tongue epithelium . ^^^ Shh expression was only observed in the suprabasal layers , whereas Ptc was observed in both basal and suprabasal layers . ^^^ Shh and Ptc expression were never detected in the mesenchyme . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Shh displays inductive , proliferative , neurotrophic and neuroprotective activities on various neural cells and signals through a receptor complex associating Patched ( Ptc ) and Smoothened ( Smo ) . ^^^ Shh binding to Ptc leads to downstream activation of target genes , such as transcription factors of the Gli family . ^^^ In the ventral neural tube , the distribution of Shh , Ptc and Smo is in agreement with this functional model . ^^^ These observations suggest that in the adult brain , Shh signals through its receptor complex Ptc / Smo , or through Ptc alone . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We quantitated the expression levels of Shh and its receptor genes , Patched ( Ptc ) and Patched 2 ( Ptch 2 ) , in two distinct experimental systems in which the development of hair follicles was suppressed . ^^^ Shh , Ptc , and Ptch 2 were induced about six to tenfold in normal embryonic hair germs in vivo as well as in developing skin tissue maintained in organ culture . ^^^ Expression of Shh , Ptc and Ptch 2 was induced in the Tabby embryos at 16 . 5 days postcoitus , indicating that Shh signaling may be involved in the formation not only of the well studied guard hair but also of the awl hair . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| This results in down regulation of Ptc , a principle target of Shh signaling . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Fine gene mapping in this study indicated that mes is tightly linked to patched ( ptc ) that encodes a transmembrane receptor protein for Shh . ^^^ Since mes homozygous embryos exhibit normal spinal cord development as compared with ptc ( ) homozygotes , which die around 10 dpc with severe neural tube defects , the C terminal cytoplasmic domain lost in mes mutation is dispensable for inhibition of Shh signaling in early embryogenesis . ^^^ These findings indicate that Ptc is a negative regulator of body weight and ectopic activation of Shh signaling in the anterior mesenchyme of the limb buds , and that the C terminal cytoplasmic domain of Ptc is involved in its repressive action . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| When SSC cells were transduced with Ptc virus , colony forming activity in soft agar was drastically reduced and these cells recovered anchorage independent growth when Sonic hedgehog ( Shh ) , the ligand of Patched ( Ptc ) , was added into the soft agar culture . ^^^ Cyclopamine , a specific inhibitor of the Shh / Ptc / Smo signaling pathway , efficiently suppressed anchorage independent growth of A 431 and KA cells . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : Sonic hedgehog ( Shh ) signal transduction involves the ligand binding Patched 1 ( Ptc 1 ) protein and a signaling component , Smoothened ( Smo ) . ^^^ A select group of compounds inhibits both Shh signaling , regulated by Ptc 1 , and late endosomal lipid sorting , regulated by the Ptc related Niemann Pick C 1 ( NPC 1 ) protein . ^^^ Ptc 1 and Smo colocalize extensively in the absence of ligand and are internalized together after ligand binding , but Smo becomes segregated from Ptc1 / Shh complexes destined for lysosomal degradation . ^^^ Ligand induced segregation allows Smo to signal independently of Ptc 1 after becoming sorted from Ptc1 / Shh complexes in the late endocytic pathway . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Absence of WNT5a activity in the mutant lungs leads to increased expression of Fgf 10 , Bmp 4 , Shh , and its receptor Ptc , raising the possibility that WNT5a , FGF 10 , BMP 4 , and SHH signaling pathways are functionally interactive . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Sonic Hedgehog ( Shh ) is a secreted morphogen that directs patterning and cellular differentiation through binding to its receptor Patched ( Ptc ) . ^^^ No reduction of Ptc 1 transcripts was observed in Shh null mammary tissues . ^^^ Our results demonstrate that neither Shh nor Ihh is required for mammary gland morphogenesis and functional differentiation , suggesting that the two members of the Hedgehog family may have redundant function in activating the Ptc 1 signaling pathway during mammary gland development . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Patched ( Ptc ) is a transmembrane receptor for sonic hedgehog ( Shh ) and functionally associated with another transmembrane protein , smoothened ( Smo ) . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| It has been postulated that binding of sonic hedgehog protein ( SHH ) to its receptor , patched protein ( PTC ) , releases the inhibitory effect of PTC against smoothened protein ( SMO ) , another protein of the SHH signalling pathway . ^^^ Recently , hedgehog interacting protein ( HIP ) was found to bind to SHH directly and attenuate SHH signalling like PTC , while its expression was induced by SHH signals . ^^^ OBJECTIVES : To examine the expression patterns of HIP , SHH and PTC gene mRNA by human BCCs , in comparison with those by normal human skin and various skin tumours . ^^^ CONCLUSIONS : These results indicate that both HIP and PTC gene expression are specifically involved in the development of BCCs , and that the production of HIP is linked with the expression of the PTC gene but not the SHH gene . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| To determine whether Gli 1 contributes to the defects seen when the Shh pathway is inappropriately activated and Gli 1 transcription is induced , Gli 1 ; Ptc double mutants were generated . ^^^ We show that Gli 1 is not required for the ectopic activation of the Shh signaling pathway or to the early embryonic lethal phenotype in Ptc null mutants . ^^^ Of significance , we found instead that Gli 2 is required for mediating some of the inappropriate Shh signaling in Ptc mutants . ^^^ Our studies demonstrate that , in mammals , Gli 1 is not required for Shh signaling and that Gli 2 mediates inappropriate activation of the pathway due to loss of the negative regulator Ptc . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| In this study , we demonstrate that Shh and its receptor Patched ( Ptc ) are expressed on resting and activated human peripheral CD 4 ( + ) T cells . ^^^ In approximately one half of the randomly selected , anonymous blood donors tested , exposure of anti CD3 / 28 Ab activated CD 4 ( + ) T cells to the biologically active N terminal Shh peptide increased the transcription of ptc , thereby demonstrating that Shh signaling had occurred . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Prior to the ectopic induction of Shh , the expression domains of genes downstream from Shh , namely dHAND , Gli 1 , Ptc and Gre , which are normally expressed in posterior mesenchyme of limb buds , expanded anteriorly on the lx hindlimb buds . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Shh signals through interaction with the tumour suppressor Patched ( Ptc ) . ^^^ The study described here shows that injection of aminoterminal myristoylated Shh ( myrShhN ) into the adult rat striatum robustly increases the levels of Ptc transcripts in selective brain areas including the subventricular zone ( SVZ ) . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| To test this hypothesis , Shh , BMP 4 , Ptc , and Hoxa 10 localization and function were examined in Sprague Dawley rat penes by means of quantitative reverse transcription polymerase chain reaction , in situ hybridization , immunohistochemistry , and Western blotting . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The mandibular cysts were immunohistochemically investigated using anti ptc , shh , and smo antibodies . ^^^ Immunohistochemical examination showed sonic hedgehog ( shh ) protein mainly in cyst lining epithelium , and ptc and smoothened ( smo ) proteins in cyst lining epithelium , and surrounding fibrous connective tissue . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Ptc protein had a similar distribution to Shh , although the immunoproduct was more diffuse . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| In addition , Shh upregulates several mesenchymal cell markers , including its target gene Patched ( Ptc ) , intercellular signaling genes Bone Morphogenetic Protein 4 ( Bmp 4 ) and Noggin ( Nog ) , and smooth muscle actin and myosin . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : Mutations of the patched ( Ptc ) gene , a developmental regulator implicated in the signalling pathway via sonic hedgehog ( Shh ) and smoothened ( Smo ) , play an essential pathogenic role in the development of basal cell carcinomas ( BCCs ) . ^^^ We previously reported the upregulation of Shh signal transducers , including Ptc , Smo and hedgehog interacting protein , in BCCs . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Furthermore , these conditions resulted in transcriptional activation of smoothened ( smo ) , patched ( ptc ) and gli 1 ; Smo , Ptc and Gli 1 , as well as cholesterol , are components of the Sonic hedgehog ( Shh ) signalling pathway , which directs pattern formation , diversification and tumourigenesis in mammalian cells . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We show that Patched ( Ptc ) induces apoptotic cell death unless its ligand Shh is present to block the signal . ^^^ Moreover , the blockade of Ptc induced cell death partly rescues the chick spinal cord defect provoked by Shh deprivation . ^^^ Thus , the proapoptotic activity of unbound Ptc and the positive effect of Shh bound Ptc on cell differentiation probably cooperate to achieve the appropriate spinal cord development . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The secreted protein Sonic hedgehog ( Shh ) and its transmembrane receptor Patched ( Ptc ) control a major signal transduction pathway in early vertebrate limb development . ^^^ Ligand bound Ptc removes the block and leads to further expression of ptc , which in turn restricts the range of Shh transport . ^^^ We develop a model to study the effects of two forms of Shh used experimentally and propose a mechanism for Shh signal transduction based on a two state model for the Ptc Smo interaction . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We found by in situ hybridization that the SHH autocrine receptor Ptch 2 is indeed expressed in dental epithelium whereas the paracrine receptor Ptc is expressed in mesenchyme . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We have demonstrated that Shh and Ptc expression correlates with growth and development of the prostate and that their expression is not regulated by androgens in the VP . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| In this study we investigated the expression of key factors in the Shh pathway , namely Shh and its receptor Patched ( Ptc ) , in normal and pathologic stomach mucosa . ^^^ Expression of Shh and Ptc was analyzed by immunohistochemistry . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| To determine whether this signaling system is important in vivo for regulating retinal progenitor proliferation , we analyzed mice with a single functional allele of the Shh receptor patched ( ptc ) . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| To address this question , we first determined the spatiotemporal distribution of Shh ; two transmembrane proteins , patched 1 ( Ptc ) and Smoothened ( Smo ) , which act as a negative or a positive regulator of the Shh signal , respectively ; and the Gli 3 transcription factor , which is downstream of the Shh signal . ^^^ The epithelial localization of Shh , Ptc , Smo , and Gli 3 suggests that Shh signaling may act within the epithelium in a juxtacrine manner . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : To clarify the roles of Sonic hedgehog ( SHH ) signal transduction in oncogenesis and cytodifferentiation of odontogenic tumors , expression of SHH , Patched ( PTC ) , Smoothened ( SMO ) , and GLI 1 was analyzed in ameloblastomas as well as in tooth germs . ^^^ METHODS : Tissue specimens of 9 tooth germs , 36 benign ameloblastomas , and 1 malignant ameloblastoma were examined by reverse transcriptase polymerase chain reaction ( RT PCR ) and immunohistochemistry for the expression of SHH , PTC , SMO , and GLI 1 . ^^^ RESULTS : Expression of SHH , PTC , SMO , and GLI 1 mRNA was detected in all tooth germ and ameloblastoma samples . ^^^ Immunohistochemical reactivity for SHH , PTC , SMO , and GLI 1 was detected in both normal and neoplastic odontogenic tissues . ^^^ Expression of SHH , PTC , and GLI 1 was more evident in epithelial cells than in mesenchymal cells , whereas SMO reactivity was marked in both epithelial and mesenchymal components in tooth germs and ameloblastomas . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Shh , the secreted signal molecule , patched ( Ptc ) , its membrane receptor , and Gli 1 , a downstream transcription factor , were detected at the gene level with semiquantitative reverse transcriptase polymerase chain reaction ( RT PCR ) and at the protein level with Western blot analysis . ^^^ EDL did not alter epididymal segmentation , but Shh , Ptc , and Gli 1 expression was significantly altered at specific times after the ligation . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| METHODS : Immunofluorescent staining and Western blot analysis were used to detect Shh , patched 1 ( Ptc 1 ) receptors , and Gli transcription factors in corneal epithelium of Wistar rats ( n = 44 ) at various intervals after an epithelial defect . ^^^ RESULTS : Uninjured rat corneal epithelium was not labeled by anti Shh antibody , but weakly positive for Ptc 1 . ^^^ Basal cells of limbal and conjunctival epithelia were labeled by antibodies against Shh and Ptc 1 . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| PTC gene mutations and expression of SHH , PTC , SMO , and GLI 1 in odontogenic keratocysts . ^^^ The Patched ( PTC ) gene is responsible for basal cell nevus syndrome ( BCNS ) accompanied by multiple odontogenic keratocysts ( OKCs ) , and its product plays a role in the Sonic hedgehog ( SHH ) signaling pathway involving smoothened ( SMO ) and GLI 1 . ^^^ To clarify the role of SHH signaling in OKCs , the expression of SHH , PTC , SMO , and GLI 1 and mutations of PTC were examined in 18 sporadic , 4 BCNS associated OKCs and 7 control gingivae . ^^^ SHH , PTC , SMO , and GLI 1 were detected in all OKC and gingiva samples by reverse transcriptase polymerase chain reaction ( RT PCR ) . ^^^ Immunoreactivity for SHH and GLI 1 was markedly higher in epithelial components than in subepithelial cells , while immunoreactivity for PTC and SMO was similar in epithelial components and subepithelial cells in OKCs . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Herein , we examined Sonic hedgehog ( Shh ) patched ( ptc ) gli in the developing rat prostate gland , its role in branching morphogenesis , and the effects of neonatal estrogens on its expression and localization to determine whether a disturbance in this signaling pathway is involved in mediating the estrogenized phenotype . ^^^ Shh was expressed in epithelial cells at the distal tips of elongating ducts in discreet , heterogeneous foci , while ptc and gli 1 3 were expressed in the adjacent mesenchymal cells in the developing gland . ^^^ Neonatal exposure to high dose estradiol suppressed Shh , ptc , gli 1 , and gli 3 expressions and concomitantly blocked ductal branching in the dorsal and lateral prostate lobes specifically . ^^^ In contrast , ventral lobe branching and Shh ptc gli expression were minimally affected by estrogen exposure . ^^^ Organ culture studies with lateral prostates confirmed that estradiol suppressed Shh ptc gli expression directly at the prostatic level . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Now we have immunolocalized the Shh protein and the Patched receptor protein ( Ptc ) , and have tested potential roles for Shh in formation of the tongue , emergence of papilla placodes , development of papilla number and size , and maintenance of papillae after morphogenesis is advanced . ^^^ Shh and Ptc proteins are diffuse in prelingual tissue and early tongue swellings , and are progressively restricted to papilla placodes and then to regions of developing papillae . ^^^ Ptc encircles the dense Shh immunoproduct in papillae at various stages . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Binding of Sonic Hedgehog ( Shh ) to Patched ( Ptc ) relieves the latter ' s tonic inhibition of Smoothened ( Smo ) , a receptor that spans the cell membrane seven times . ^^^ Ptc inhibits association of beta arrestin 2 with Smo , and this inhibition is relieved in cells treated with Shh . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We have recently shown that developmental expression of Shh ptc gli is downregulated in the dorsolateral prostate following estrogenization , and this is responsible , in part , for branching deficits observed in that prostatic region specifically . ^^^ Fgf 10 and FgfR2iiib localize to the distal signaling center of elongating and branching ducts in separate prostate lobes where they regulate the expression of multiple morphoregulatory genes including Shh , ptc , Bmp 7 , Bmp 4 , Hoxb 13 , and Nkx3 . 1 . ^^^ Similar to Shh ptc gli , neonatal estrogen exposure downregulates Fgf 10 , FgfR2iiib , and Bmp 7 expression in the dorsolateral prostate while ventral lobe expression of these genes is unaffected . ^^^ Together , these studies demonstrate that alterations in Fgf 10 signaling are a proximate cause of Shh ptc gli and Bmp 7 downregulation that together result in branching inhibition of the dorsolateral prostate following neonatal estrogen exposure . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| However , overexpression of shh does not increase median pituitary placode size nor does it upregulate patched ( ptc ) expression in pituitary precursors during early somitogenesis . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| This effect of Shh was not mediated by Patched ( Ptc ) and Smoothened ( Smo ) , the receptors that mediate effects of Shh in morphogenesis and commissural axon growth toward the floor plate . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Expression of activated EGFR causes pre and postaxial polydactyly , including mirror image type digit duplication , likely due to induction of ectopic expression and / or modulation of genes involved in anterior posterior ( AP ) patterning such as Sonic hedgehog ( Shh ) , dHand , Patched ( Ptc ) , Gli 3 , Hoxd 13 , Hoxd 11 , bone morphogenetic protein 2 ( Bmp 2 ) , Gremlin , and FGF 4 . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| During the same developmental period Noggin mRNA is highly expressed throughout the spine , in the developing AF , while ptc protein and SHH mRNA were expressed in the developing nucleus pulposus ( NP ) . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| For example , Shh was not induced in the frontonasal ectoderm , and Ptc and Gli 1 were reduced in both the ectoderm and adjacent mesenchyme . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Xenotransplants were characterized with histochemistry ( HE , PAS ) , immunohistochemistry ( cytokeratin ( CK ) 7 , CK 8 , CK 18 , CK 19 , CK 20 , vimentin , chromogranin A ( Chr A ) , alpha 1 antichymotrypsin ( alpha 1 chym ) , beta catenin , laminin 5 , pancreatic and duodenal homeobox gene 1 ( pdx 1 ) , sonic hedgehog protein ( shh ) , Patched ( ptc ) ) , Western blotting and real time PCR ( CK 7 , CK 8 , CK 20 , Chr A , pdx 1 , shh , ptc ) . ^^^ Predominantly the CK 7 positive ductal phenotype ( YAPC and DAN G ) was associated with pdx 1 expression , whereas the CK 8 positive solid phenotype was associated with shh / ptc expression on protein and mRNA level . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Both levels and distribution of SHH receptor , Ptc were reduced in SpC Wnt5a transgenic lungs and were reciprocally correlated to changes of Fgf 10 in the mesenchyme , suggesting that SHH signaling is decreased by over expression of Wnt5a . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Our results suggest that both acute and chronic ECS enhance Shh signalling in the adult hippocampus , as we observed a robust upregulation of Patched ( Ptc ) mRNA , a component of the Shh receptor complex and a downstream transcriptional target of Shh signalling . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The initial part of this process is accomplished by Shh acting through Patched ( Ptc ) to regulate Smoothened ( Smo ) activity . ^^^ Recently , a forward genetic approach in mice identified a role for intraflagellar transport ( IFT ) genes in Shh signal transduction , downstream of Patched ( Ptc ) and Rab 23 . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The morphogen , Sonic hedgehog ( Shh ) , is a crucial regulator of these processes , along with its down stream targets patched ( Ptc ) , Hox , bone morphogenetic proteins ( BMP ' s ) , vascular endothelial growth factor ( VEGF ) and nitric oxide synthase ( NOS ) . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| In mice , disruption of Ink4c collaborates independently with loss of p 53 or with inactivation of the gene ( Ptc 1 ) encoding the Shh receptor , Patched , to induce MB formation . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Abbreviations used : BrdU , 5 bromo 2 ' deoxyuridine ; HERS , Hertwig ' s epithelial root sheath ; NFI C / CTF , nuclear factor Ic / CAAT box transcription factor ; PCNA , proliferating cell nuclear antigen ; Ptc , patched ; Shh , sonic hedgehog ; Smo , smoothened . . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The transmembrane receptor Patched ( Ptc ) mediates the action of the diffusing factor Sonic hedgehog ( Shh ) , which is implicated in establishing morphogenetic gradients during embryonic development . ^^^ Here we describe the complementary pattern of Shh and Ptc expression in the rat dorsal vagal motor nucleus and the ventrolateral nucleus tractus solitarius ( vNTS ) , respectively . ^^^ Both inhibiting and bursting effects are blocked by the monoclonal Shh antibody 5E1 and may require the Ptc binding site of ShhN . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Purified protein was assayed for biological activity and found to activate the transcription of the Patched genes ( Ptc 1 and Ptc 2 ) encoding receptors for SHH . . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We demonstrate co localization of the Patched 1 ( Ptc 1 ) receptor and its ligand sonic hedgehog ( Shh ) in lysosomes suggests an intracellular sorting mechanism for this receptor and its ligand . ^^^ Treatment of murine brain primary cultures and a human teratoma cell line with the N terminal activated form of Shh ( ShhNT ) , a Ptc 1 Shh complex was observed in lysosomes . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Dorsally expressed Shh signals induce ectopic transcription of its receptor Ptc 1 in the midbrain and the hindbrain . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Furthermore , addition of the ptc 1 ligand , sonic hedgehog ( shh ) , disrupts this interaction and allows cyclin B 1 to localize to the nucleus . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We show that Smo acts epistatic to Ptc 1 to mediate Shh and Ihh signaling in the early mouse embryo . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| They first appear within a region of anterior hypothalamic neuroepithelium that co expresses mRNA encoding SHH , its receptor PTC 1 ( PTCH ) and the transcription factors OLIG 1 , OLIG 2 and SOX 10 . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| A subset of cells in the basal layer of the epidermis in close proximity to the newly formed dermal bone structures of the fin rays , the lepidotrichia , express shh , and ptc 1 which is thought to encode the receptor of the SHH signal . ^^^ The expression domain of ptc 1 is broader than that of shh and adjacent blastemal cells releasing the dermal bone matrix also express ptc 1 . ^^^ Further observations indicate that the bmp 2 gene , in addition to being expressed in the same cells of the basal layer of the epidermis as shh , is also expressed in a subset of the ptc 1 expressing cells of the blastema . ^^^ Amputations of caudal fins immediately after the first branching point of the lepidotrichia , and global administration of all trans retinoic acid , two procedures known to cause fusion of adjacent rays , result in a transient decrease in the expression of shh , ptc 1 and bmp 2 . ^^^ These observations suggest a role for shh , ptc 1 and bmp 2 in patterning of the dermoskeleton of developing and regenerating teleost fins . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The expression of Gli 1 and Ptc 1 was reduced in Shh / dermal condensates and they failed to evolve into hair follicle papillae , suggesting that the adjacent mesenchyme is a critical target for placode derived Shh . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Sonic hedgehog ( Shh ) , one of the vertebrate homologs of Hh , controls patterning and growth of the limb but the early embryonic lethality of ptc 1 ( ) ( / ) ( ) mice obscures the roles of ptc 1 in later stages of development . ^^^ The polydactyly was preceded by unexpected anterior limb bud transcription of Shh , so one function of ptc 1 is to repress Shh expression in the anterior limb bud . . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We have performed a time course analysis of the expression of Sonichedgehog ( shh ) and patched 1 ( ptc 1 ) in response to exogenous retinoic acid ( RA ) application to get some insight into the mechanism ( s ) underlying the formation of a mirror image duplication of shh and ptc 1 domains of expression in the pectoral fin buds of zebrafish . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We have investigated the expression of Hip during early tooth development and found it not to be localized in cells immediately adjacent to Shh expressing cells , but rather at a distance , separated by cells expressing Ptc 1 . ^^^ A role for Hip might be to prevent the spread of excess Shh ligand beyond an immediate Ptc 1 induced zone in odontogenic mesenchyme . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| It differs from other polydactylous mutants in showing normal Shh expression , but polarizing activity ( shown by mouse chick grafting experiments ) and hedgehog signalling activity ( shown by expression of Ptc 1 ) are present throughout the distal mesenchyme . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The Patchedl ( Ptc 1 ) protein is a receptor for Sonic hedgehog ( Shh ) , a secreted protein ligand . ^^^ Ptc 1 limits the effects of the Shh signal , so mutations in PTCH may lead to persistent granule cell precursors susceptible to further genetic or environmental events that cause medulloblastoma . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Here we show that Shh and its receptor , Ptc 1 , are expressed in the adult rat basal forebrain , and that Ptc 1 is expressed specifically by cholinergic neurons . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Shh was similarly expressed in the floor plate of the mutant hindbrain , while the expressions of Ptc 1 , Gli 1 and Gli 2 were altered only in the progenitor domains for the motoneurones . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Morphological changes were accompanied by an expansion , followed by a reduction , in domains of shh expression and a rapid abolition of ptc 1 expression . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| In heterozygous ptc 1 cells , ptc 1 lacZ was expressed at low levels but could be induced by Sonic Hedgehog ( Shh ) and Gli 1 . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The gene for the Shh receptor , Ptc 1 , is expressed in the UGM , as are the members of the Gli gene family of transcriptional regulators ( Gli 1 , Gli 2 , and Gli 3 ) . ^^^ A strong dependence of Gli 1 ( and Ptc 1 ) expression on Shh signaling is demonstrated by induction of expression in both the intact urogenital sinus and the isolated UGM by exogenous SHH peptide . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The Shh receptors Ptc 1 ( Patched 1 ) and Ptc 2 were found to be expressed in prostatic stromal cells adjacent to the epithelium , where Shh itself was produced . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Mutants lacking Patched 1 ( Ptc 1 ) , the putative receptor of Shh , were used to analyze Gli functions . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Expression of Shh , Ptc 1 , Ptc 2 mRNA in the cap stage of mouse molar ] . ^^^ OBJECTIVE : To investigate the expression of Shh and its receptors Ptc 1 and Ptc 2 mRNA in the cap stage of mouse molar and discuss its role in early tooth morphogenesis . ^^^ The expression pattern of Shh , Ptc 1 , and Ptc 2 mRNA was analysed by in situ hybridization . ^^^ Shh , Ptc 1 , and Ptc 2 mRNA were strongly expressed in outer dental epithelium , inner dental epithelium , stellate reticulum and the enamel knot . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The authors aimed to study the temporal and spatial pattern of expression of Shh and its receptor Ptc 1 during the development of the anterior foregut and to test the hypothesis that the Shh expression pattern is disturbed during the development of oesophageal atresia ( OA ) and tracheo oesophageal fistula ( TOF ) in Adriamycin treated mouse embryos . ^^^ METHODS : Saline and Adriamycin treated ( 4 mg / kg ) CBA / Ca embryos were harvested between embryonic days ( E ) 10 . 5 and 12 . 5 , and Shh and Ptc 1 expression was studied by whole mount and section in situ hybridisation using digoxygenin labelled riboprobes . ^^^ Ptc 1 was expressed in the mesoderm adjacent to Shh expressing endoderm at both stages . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| In addition , the Ptc 1 receptor is activated in interstitial mesenchymal cells within the ischemic area , indicating that these cells respond to Shh and that the Shh pathway is functional . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We show that at these stages in the murine mandibular arch in the absence of epithelium , the Shh targets Ptc 1 and Gli 1 are upregulated in diastema mesenchyme , an edentulous region between the sites of molar and incisor tooth formation . ^^^ Although Shh signalling has no effect upon Gas 1 expression in mandibular arch mesenchyme , overexpression of Gas 1 results in downregulation of ectopic Ptc 1 . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| METHODS : Inhibition of Hh signaling by HIP was assayed by measuring the induction of Ptc 1 mRNA in TM 3 cells treated with conditioned medium containing Sonic hedgehog ( Shh ) . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The expression of SHH receptor , Patched 1 ( Ptc 1 ) , was greatly increased in all cartilage , as well as the expression of parathyroid hormone related protein ( PTHrP ) at the articular surface ; while the expression of Indian Hedgehog ( Ihh ) , another member of Hh family that controls the rate of chondrocyte maturation , was greatly reduced and restricted to the displaced chondrocyte columns . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc 1 ( + / ) p 53 ( / ) mice . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We show that Shh expression domains are lost from the talpid ( 3 ) head in hindbrain , midbrain , zona limitans intrathalamica , and stomodeal ectoderm and that direct targets of Hedgehog signaling , Ptc 1 , Ptc 2 , and Gli 1 , are also absent even in areas associated with primary Shh expression . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Constitutive activation of the shh ptc 1 pathway by a patched 1 mutation identified in BCC . ^^^ The ptc 1 Q688X mutant enhances Gli 1 activity , a downstream reporter of sonic hedgehog ( shh ) ptc 1 signaling , independent of shh stimulation . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Shh and its mediators Ptc 1 , Ptc 2 , and Gli 1 were down regulated only in the lower but not the upper molars of Runx 2 and Runx2 / Runx3 knockouts . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| A growing list of diverse antagonists have been identified that restrict Shh signalling in the embryo , however , only Ptc 1 , Gas 1 and Hip 1 have been studied during tooth development . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| In monolayer P 19 ( Shh ) cultures the Shh pathway was functional as shown by the up regulation of Ptc 1 and Gli 1 expression , but no cardiac muscle markers were activated . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Patched 1 ( Ptc 1 ) functions as a receptor for Sonic hedgehog ( Shh ) in a wide range of biological processes . ^^^ Binding of Shh to Ptc 1 results in activation of Smoothened ( Smo ) , which in turn stimulates expression of downstream target genes including Ptc 1 and Gli 1 . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| METHODS : Using immunohistochemistry , we determined the expression of Shh and its receptors Patched 1 ( Ptc 1 ) and Patched 2 ( Ptc 2 ) in 55 human pituitary adenomas compared with the normal pituitary gland . ^^^ RESULTS : Ptc 1 and Ptc 2 were present , whereas Shh was down regulated in pituitary adenomas and completely absent in Cushing tumors . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The receptor Ptc 1 and a regulator of Hh signalling Hhip 1 are expressed in the mesenchyme adjacent to the palatal oral epithelium so that the highest level of transcripts localize to the palatal mesenchyme surrounding the Shh expressing thickened epithelium . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Hh agonist induced hair growth caused no detectable differences in epidermal proliferation , differentiation , or in the endogenous Hh signaling pathway as measured by Gli 1 , Shh , Ptc 1 , and Gli 2 gene expression when compared with a normal hair cycle . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| This is accompanied by a severe depletion of medial cell populations that encounter high concentrations of SHH , an expansion of lateral cell populations that experience low concentrations of SHH and a broad deregulation of HH ' s principal effectors ( PTC 1 , GLI 1 , GLI 2 , GLI 3 ) . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| In contrast , mice lacking one or two functional Ink4c alleles and one copy of Patched ( Ptc 1 ) encoding the Shh receptor rapidly developed MBs that retained wild type p 53 . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Hedgehog interacting protein ( Hip ) and Patched 1 ( Ptc 1 ) regulate the cell responses to the morphogen Sonic Hedgehog ( Shh ) . ^^^ Here , we compare the relative expression patterns of Shh , Hip and Ptc 1 transcripts in the E13 . 5 mouse brain embryo . ^^^ We observe that the expression of Hip and Ptc 1 often overlaps and is found close to Shh expressing cells , suggesting that both proteins are required for controlling Shh signals . ^^^ These data raise the hypothesis for a functional link between nitric oxide and Shh signaling and for a nonredundant role of Hip and Ptc 1 in the adult brain . . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The expression patterns of the Sonic hedgehog signaling cascade genes ( Shh , Ptc 1 and Gli 1 ) were mostly unchanged in the in situ hybridization , but the quantitative expressions of Ptc 1 and Gli 1 were increased in real time reverse transcriptase polymerase chain reaction analyses , quite contrary to the findings of a previous study using chick embryos . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Stimulation of wild type MEFs by Sonic Hedgehog ( Shh ) peptide elicited unique profiles of induction of Hedgehog target genes Gli 1 , Ptc 1 , and Hip 1 . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| METHODS AND RESULTS : We first found that Shh , its receptors Patched 1 ( Ptc 1 ) as well as Smoothened ( Smo ) and its downstream transcription factor Gli 1 were expressed in the basal layer of human fetal epidermis and freshly sorted HPESCs . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Therefore , CUSP appears to be present , unmutated , and yet frequently undetectable by immunofluorescence in cutaneous lesions in both humans and mice that are associated with SHH pathway dysregulation ( BCCs , BCNS , and nevus sebaceous ) . . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Individuals with germline mutations of the SHH receptor gene PTCH are at high risk of developmental anomalies and of basal cell carcinomas , medulloblastomas and other cancers ( a pattern consistent with nevoid basal cell carcinoma syndrome , NBCCS ) . ^^^ |
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| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The binding of Sonic hedgehog ( SHH ) to its receptor , PTCH , is thought to prevent normal inhibition by PTCH of Smoothened ( SMO ) , a seven span transmembrane protein . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The PTCH gene product ( Ptch ) functions as a transmembrane receptor for the Sonic hedgehog protein ( Shh ) and interacts with another transmembrane protein called Smoh . ^^^ To further elucidate the significance of alterations in the Shh signaling pathway , we investigated 31 sporadic BCCs and 15 PNETs for the mutation and / or expression of SMOH , PTCH , SHH , and GL 11 . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The multitransmembrane protein Patched ( PTCH ) is the receptor for Sonic Hedgehog ( Shh ) , a secreted molecule implicated in the formation of embryonic structures and in tumorigenesis . ^^^ Current models suggest that binding of Shh to PTCH prevents the normal inhibition of the seven transmembrane protein Smoothened ( SMO ) by PTCH . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Overlapping and non overlapping Ptch 2 expression with Shh during mouse embryogenesis . ^^^ In the developing tooth , hair and whisker , Shh and Ptch 2 are co expressed in the epithelium while Ptch is strongly expressed in the mesenchymal cells . ^^^ In early mouse embryos , Ptch and Ptch 2 were found to be co expressed in regions adjacent to Shh expressing cells in the developing CNS . ^^^ Similar to other epidermal structures , Shh and Ptch 2 also show overlapping expression in the developing nasal gland and eyelids . ^^^ Thus , during mouse development , Ptch 2 is expressed in both Shh producing and nonproducing cells . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The patched / hedgehog / smoothened signalling pathway in human breast cancer : no evidence for H133Y SHH , PTCH and SMO mutations . ^^^ A substantial proportion of breast carcinomas has recently been suggested to contain missense mutations in the human patched ( PTCH ) and sonic hedgehog ( SHH ) homologues . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Analysis of PTCH / SMO / SHH pathway genes in medulloblastoma . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Syndrome related disorders have been attributed to alterations of PTCH gene , which plays an important role in Shh signalling pathway . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Constitutional hemizygous inactivation of PTCH , the Shh signaling pathway gene that moderates the signal , manifests itself as nevoid basal cell carcinoma syndrome or Gorlin syndrome , a condition variably characterized by a number of developmental disorders and malformations , and by predisposition to some malignancies , basal cell carcinoma in particular . ^^^ Suggestive temporal distribution of Shh signaling , recently observed during tooth development , lead us to investigate PTCH association with dentigerous cysts , the other major noninflammatory cyst of odontogenic origin . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The abnormalities are associated with congenital or sporadic genetic alteration affecting function of different components of the HH signaling pathway , including SHH , PTCH , SMOH and GLI proteins . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Here we tested the genetic interaction between Sil and the Shh pathway by generating and analyzing embryos carrying mutations in both Sil and Patched ( Ptch ) , a Shh receptor that normally inhibits the signaling pathway in the absence of ligand and when mutated leads to constitutive activation of the pathway . ^^^ We find that Sil ( / ) Ptch ( / ) embryos do not activate the Shh pathway and instead have a phenotype indistinguishable from Sil ( / ) embryos , in which there is a loss of activity of Shh . ^^^ These results provide genetic evidence that Sil is an essential component of the Shh response , acting downstream to Ptch . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| PATCHED 1 ( PTCH ) , the receptor for SHH , normally acts to repress SHH signaling . ^^^ This repression is relieved when SHH binds to PTCH . ^^^ We predict that by enhancing the repressive activity of PTCH on the SHH pathway , these mutations cause decreased SHH signaling , and HPE results . ^^^ The mutations could affect the ability of PTCH to bind SHH or perturb the intracellular interactions of PTCH with other proteins involved in SHH signaling . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We also find that Ta mutants lack completely the placodes of the first developing tylotrich hairs , and that they do not show patterned expression of placodal genes , including Bmp 4 , Lef 1 , Shh , Ptch and Edar , and the genes for beta catenin and activin A . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| This is accompanied by disruption of the expression of genes ( Shh , Gli 1 , Gli 2 , Gli 3 , and Ptch ) associated with SHH signalling in the limb bud mesenchyme , the down regulation of Bmp 4 in the apical ectoderm , the absence of Alx 3 , Alx 4 , Pax 1 , and Pax 3 activity in the mesenchyme , and a reduced potency of the limb bud tissues to differentiate into osteogenic and myogenic tissues . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The sonic hedgehog ( SHH ) patched ( PTCH ) pathway functions in normal embryonic development of the brain , musculoskeletal system , and hair follicles , and in normal post natal control of hair follicles . ^^^ Based on the knowledge that generalized , prolonged PTCH expression can inhibit the effects of SHH signaling , we tested the hypothesis that localized transient overexpression of PTCH would inhibit the phenotype of SHH induced accelerated growth of hair follicles . ^^^ Thus , PTCH expression mediated by gene transfer can modulate the SHH signaling pathway in the adult mammal and may serve as a starting point for therapies relevant to clinical conditions resulting from dysregulation of this pathway as well as for strategies to suppress normal SHH dependent processes , such as hair growth . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Disorders of the sonic hedgehog signaling network are discussed next , including holoprosencephaly and the nevoid basal cell carcinoma syndrome , the former being caused by sonic hedgehog ( SHH ) mutations and the latter being caused by patched mutations ( PTCH ) . . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Accompanying overexpression of beta catenin is up regulation of Sonic hedgehog ( SHH ) and its receptor , Patched ( PTCH / Ptch ) . ^^^ In DeltaNLef 1 tumors Ptch mRNA is up regulated in the absence of SHH . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Mutations of the Shh receptor PATCHED ( PTCH ) are associated with medulloblastomas , which have not been found to have loss of PTCH heterozygosity . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Basal cell carcinomas are characterized by aberrant activation of Sonic Hedgehog ( SHH ) signaling due to mutations in the PTCH or SMOH genes . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We also demonstrate linked overexpression of BMI 1 and patched ( PTCH ) , suggestive of SHH pathway activation , in a substantial fraction of primary human medulloblastomas . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Sonic hedgehog ( Shh ) binds to its receptor patched ( PTCH ) , leading to the activation and repression of target genes via the GLI family of zinc finger transcription factors . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| In the cerebellum from IFN gamma expressing but not age matched non IFN gamma expressing mice , the level of Shh and Gli 1 but not Patched ( Ptch ) 1 RNA was increased as was the 19 kDa signaling product of the Shh precursor protein . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| PTCH , a 12 pass transmembrane protein , is a receptor for Sonic hedgehog ( Shh ) signaling proteins . ^^^ Shh proteins activate transcription of target genes , including PTCH , via GLI transcription factors . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| A total of 106 uterine cervical cancers and related lesions ( 37 squamous cell carcinomas , 23 cervical intraepithelial neoplasia ( CIN ) 3 , 10 CIN 2 , four CIN 1 , 32 normal cervical epithelia ) were immunohistochemically analyzed with anti Shh , Indian Hh ( Ihh ) , Patched ( PTCH ) , Smoothened ( Smo ) , Gli 1 , Gli 2 , Gli 3 antibodies on paraffin blocks . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| IHH , SHH , Patched ( PTCH ) , Smoothened ( SMO ) , and downstream targets were expressed more frequently and highly in the diffuse as compared with intestinal type cancers . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The understanding of mutations that are known to activate hedgehog ( Hh ) signalling pathway genes , including PATCHED ( PTCH ) , sonic hedgehog ( Shh ) and smoothened ( Smo ) , has substantially expanded our current understanding of the genetic basis of BCC development . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Functional analysis by organ culture revealed that Shh could regulate mesenchymally expressed genes , patched 1 ( Ptch 1 ) , bone morphogenetic protein 4 ( Bmp 4 ) , Hoxd 13 and fibroblast growth factor 10 ( Fgf 10 ) , in the anlage : the genital tubercle ( GT ) . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Furthermore , functional assays demonstrated that whereas all PTCH 1 isoforms can inhibit the activity of SHH , only the PTCH1B isoform is capable of fully inhibiting Smoh activity . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The pathways we focus on in this review are : ( 1 ) P 16 ( INK4A ) CDK4 / 6 RB ; ( 2 ) P 14 ( ARF ) HDM 2 P53 ; ( 3 ) Sonic hedgehog ( SHH ) / GLI ; ( 4 ) WNT / beta catenin ; and ( 5 ) Bone Morphogenetic Protein ( BMP ) / SMAD . 70 80 % of XP skin cancers exhibit one or several mutations in the P 53 , PTCH 1 , SMO or CDKN2A genes , the type and frequency of mutated genes being different between squamous cell ( SCCs ) and basal cell carcinomas ( BCCs ) . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| PTCH 2 promoter regulation assays demonstrated that only one of the PTCH 2 variants could inhibit the activity of SHH N , whereas none was capable of inhibiting the activated form of SMO ( SMO M 2 ) and this contrasts with PTCH 1 . ^^^ Using Ptch 1 / mouse cells , it was shown that the PTCH 2 variants and PTCH 1 differentially act to reconstitute not only the SHH but also the Desert HH dependent transcriptional response . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The roles of crucial factors identified from relevant animal model systems , including BMP 4 and SHH , and the likely events perturbed by key genes pinpointed in human studies [ such as PVRL 1 , IRF6p63 , MID 1 , MSX 1 , and PTCH 1 ] are discussed in this light . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Through genetic combinations with null alleles of patched 1 ( Ptch 1 ) , sonic hedgehog ( Shh ) and Indian hedgehog ( Ihh ) , we demonstrate that Disp 1 genetically interacts with Hh signaling components . ^^^ Conversely , increasing available Shh ligand by decreasing Ptch 1 dosage leads to the restoration of ventral cell types in Disp 1 ( Delta2 / Delta2 ) mutants . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Furthermore , expression of sonic hedgehog protein is detected in majority of PTCH 1 positive tumors ( 24 out of 27 ) . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Accordingly , GLI 1 3 and PTCH 1 mRNAs were expressed at moderate levels , and sonic hedgehog ( SHH ) mRNA expression was low to undetectable . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Signals of Hedgehog family proteins ( SHH , IHH and DHH ) are transduced through Patched family receptors ( PTCH 1 and PTCH 2 ) and Smoothened ( SMO ) to GLI family transcription factors ( GLI 1 , GLI 2 and GLI 3 ) . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Sonic hedgehog ( SHH ) , Desert hedgehog ( DHH ) and Indian hedgehog ( IHH ) bind to Patched family receptors ( PTCH 1 and PTCH 2 ) to transduce signals to GLI 1 , GLI 2 and GLI 3 . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Herein , we quantitatively confirm that expression of Shh , Ptch 1 , and Gli 3 are unaltered by teratogen exposure and demonstrate that sonic hedgehog ( Shh ) translation is unaffected . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The sonic hedgehog ( Shh ) transcript is localized to the cancer tissue , whereas expression of Gli 1 and PTCH 1 is observed both in the cancer and in the surrounding stroma . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Sonic hedgehog ( Shh ) expression is normal , yet Ptch 1 and Gli 1 , two known targets of Hh signaling , are greatly reduced , consistent with loss of Shh signaling . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| While the sonic hedgehog ( Shh ) transcript is localized to the tumor tissue , expression of Gli 1 and PTCH 1 is observed both in the tumor and in the stroma . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Human SHH , IHH , DHH ( Hedgehog homologs ) , HHAT ( Hedgehog acyltransferase ) , HHIP ( Hedgehog interacting protein ) , DISP 1 , DISP 2 , DISP 3 ( Dispatched homologs ) , PTCH 1 , PTCH 2 ( Patched homologs ) , SMO ( Smoothened homolog ) , KIF 27 , KIF 7 ( Costal 2 homologs ) , STK 36 ( Fused homolog ) , SUFU ( SuFu homolog ) , DZIP 1 ( Iguana homolog ) , GLI 1 , GLI 2 and GLI 3 ( Cubitus interruptus homologs ) are implicated in the Hedgehog signaling . ^^^ SHH up regulation , IHH upregulation and HHIP down regulation lead to aberrant activation of Hedgehog signaling through PTCH 1 to GLI 1 in gastric cancer . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Mutations of the Sonic hedgehog ( SHH ) receptor , Patched 1 ( PTCH 1 ) , have been identified in a variety of tumors . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We detect expression of Shh , PTCH 1 and Gli 1 in 115 cases of HCC and in 44 liver tissues adjacent to the tumor . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| Though mutations of the genes , PTCH 1 and SMO , are known to be involved in aberrant Shh signalling , the distinct downstream effectors of these genes are poorly described . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The Shh receptor Patched 1 ( Ptch 1 ) and its downstream effector Smoothened ( Smo ) were initial prime suspects as they are membrane proteins whose cellular dynamics are modulated by the Shh signal . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| We found that the expression of these genes was markedly induced while that of Shh or Ptch 1 , Ptch 2 was not . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| The sonic hedgehog ( SHH ) receptor Patched 1 ( Ptch 1 ) is critical for embryonic development , and its loss is linked to tumorigenesis . ^^^ |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13635 and Q15465 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.54552002 |
| The structure activity data provide a unique view of the interactions between Shh and Ptc that is not readily attainable by conventional mapping strategies . . 0.54552002^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| PTC , a vertebrate homolog of this Drosophila gene , is genetically downstream of Sonic hedgehog ( Shh ) in the limb bud . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We show that Ptc can form a physical complex with a newly cloned vertebrate homologue of the Drosophila protein Smoothened ( vSmo ) , and that vSmo is coexpressed with vPtc in many tissues but does not bind Shh directly . ^^^ These findings , combined with available genetic evidence from Drosophila , support the hypothesis that Ptc is a receptor for Shh , and that vSmo could be a signalling component that is linked to Ptc . . ^^^ Here we describe binding studies using labelled Shh that strongly suggest that the Hh receptor is encoded by patched ( ptc ) , a gene first identified in genetic screens in Drosophila . . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Beginning around 16 . 5 dpc , when Shh and Ptc RNA levels are normally both declining , this treatment caused an increase in the ratio of interstitial mesenchyme to epithelial tubules in transgenic compared to normal lungs . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Gene regulatory relationships defined in the fruit fly Drosophila suggest that overproduction of Sonic hedgehog ( SHH ) , the ligand for PTC , will mimic loss of ptc function . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Ihh has biological properties similar to those of Sonic hedgehog ( Shh ) , including the ability to regulate the conserved targets Patched ( Ptc ) and Gli . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We also show that Gli is expressed ectopically along with Ptc and Shh in Strong ' s luxoid mutant mice . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The transcript of Ptc , the putative receptor for Shh protein , can be detected anteriorly as well . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| In Drosophila , HH acts by inactivating PTC function , raising the possibility that overexpression of Sonic Hedgehog ( SHH ) in human epidermis might have a tumorigenic effect equivalent to loss of PTC function . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Further , ectopic expression of Gli 1 in the dorsal midbrain and hindbrain of transgenic mice mimics the effects of ectopically expressed Shh N , leading to the activation of ventral neural tube markers such as Ptc , HNF 3beta , and Shh ; to the suppression of dorsal markers such as Pax 3 and AL 1 ; and to the formation of ectopic dorsal clusters of dopaminergic and serotonergic neurons . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The PATCHED ( PTC ) gene encodes a Sonic hedgehog ( Shh ) receptor and a tumor suppressor protein that is defective in basal cell nevus syndrome ( BCNS ) . ^^^ Two Shh target genes , ptc itself and Gli , were derepressed in the ectoderm and mesoderm but not in the endoderm . ^^^ Thus Ptc appears to be essential for repression of genes that are locally activated by Shh . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Expression of Gli and Gli 3 , but not of Gli 2 , is subsequently downregulated at the canalicular stage , coincident with a decline in the expression of sonic hedgehog ( Shh ) and the hedgehog receptor gene , patched ( Ptc ) . ^^^ Overexpression of Shh in the lung results in increased levels of Ptc mRNA . ^^^ Gli , but not Gli 2 , is also upregulated , suggesting a differential involvement of the Gli genes in the regulation of Ptc by SHH during lung development . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Familial BCCs and a fraction of sporadic BCCs have lost the function of Patched ( Ptc ) , a Sonic hedgehog ( Shh ) receptor that acts negatively on this signalling pathway . ^^^ Moreover , loss of Ptc or overexpression of Shh can not be the sole causes of Gli 1 induction and sporadic BCC formation , as they do not occur consistently . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The binding of Sonic hedgehog ( SHH ) to its receptor , PTCH , is thought to prevent normal inhibition by PTCH of Smoothened ( SMO ) , a seven span transmembrane protein . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The mutant gene product is sufficient to fulfil the signalling properties of Shh including upregulation of the direct Shh target genes Ptc and Gli , and induction of the downstream target genes Bmp 2 , Fgf 4 and Hoxd 13 . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Interestingly , Shh and Ptc started to be expressed in patched pattern along the osteogenic fronts at the end of embryonic development and , at this time , the expression of Bmp 4 and sequentially those of Msx 2 and Bmp 2 were reduced , and they also acquired patched expression patterns . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Within the cerebellum , Shh , Ptc , and Smo transcripts were colocalized in the Purkinje cell layer . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Here we show that the feather tract is initiated by a continuous stripe of Shh , Fgf 4 , and Ptc expression in the epithelium , which then segregates into discrete feather primordia that are more strongly Shh and Fgf 4 positive . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The PTCH gene product ( Ptch ) functions as a transmembrane receptor for the Sonic hedgehog protein ( Shh ) and interacts with another transmembrane protein called Smoh . ^^^ To further elucidate the significance of alterations in the Shh signaling pathway , we investigated 31 sporadic BCCs and 15 PNETs for the mutation and / or expression of SMOH , PTCH , SHH , and GL 11 . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We report that the expression of known Shh responsive genes such as Ptc and Gli 1 is downregulated in mutant mice lacking Gli 2 function . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Virally mediated misexpression of Shh results in ectopic upregulation of its receptor Ptc and a cellular proliferation throughout the gut mesoderm . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The expression of genes involved in the Sonic Hedgehog signalling pathway , including Shh , Ptc , Smo , Gli 1 , Gli 2 and Gli 3 , were found to be expressed in temporal and spatial patterns during early murine tooth development , suggestive of a role in early tooth germ initiation and subsequent epithelial mesenchymal interactions . ^^^ Of these Ptc , Smo , Gli 1 , Gli 2 and Gli 3 were expressed in epithelium and mesenchyme whereas Shh was only detected in epithelium . ^^^ Ectopic application of Shh protein to mandibular mesenchyme induced the expression of Ptc and Gli 1 . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| A subset of cells in the basal layer of the epidermis in close proximity to the newly formed dermal bone structures of the fin rays , the lepidotrichia , express shh , and ptc 1 which is thought to encode the receptor of the SHH signal . ^^^ The expression domain of ptc 1 is broader than that of shh and adjacent blastemal cells releasing the dermal bone matrix also express ptc 1 . ^^^ Further observations indicate that the bmp 2 gene , in addition to being expressed in the same cells of the basal layer of the epidermis as shh , is also expressed in a subset of the ptc 1 expressing cells of the blastema . ^^^ Amputations of caudal fins immediately after the first branching point of the lepidotrichia , and global administration of all trans retinoic acid , two procedures known to cause fusion of adjacent rays , result in a transient decrease in the expression of shh , ptc 1 and bmp 2 . ^^^ These observations suggest a role for shh , ptc 1 and bmp 2 in patterning of the dermoskeleton of developing and regenerating teleost fins . . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Whereas Shh and Wnt10b can induce general Hedgehog and Wnt targets , Ptc and Gli for Shh and Lef 1 for Wnt10b , only Bmp 2 is able to induce tooth specific expression of Msx 1 . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The multitransmembrane protein Patched ( PTCH ) is the receptor for Sonic Hedgehog ( Shh ) , a secreted molecule implicated in the formation of embryonic structures and in tumorigenesis . ^^^ Current models suggest that binding of Shh to PTCH prevents the normal inhibition of the seven transmembrane protein Smoothened ( SMO ) by PTCH . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The expression of Gli 1 and Ptc 1 was reduced in Shh / dermal condensates and they failed to evolve into hair follicle papillae , suggesting that the adjacent mesenchyme is a critical target for placode derived Shh . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The distribution of mRNA for patched ( ptc ) , the membrane receptor for shh , was also indistinguishable between both groups . ^^^ These data show that maternal cocaine treatment during early neural tube development does not significantly alter the expression patterns of shh or ptc mRNA . ^^^ Thus , congenital defects and behavioral abnormalities associated with maternal cocaine use do not appear to result from altered expression of the shh ptc pathway . . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Genetic and biochemical data suggest that the Sonic hedgehog ( Shh ) receptor is composed of at least two proteins : the tumor suppressor protein Patched ( Ptc ) and the seven transmembrane protein Smoothened ( Smo ) . ^^^ RESULTS : Using a biochemical assay for activation of the transcription factor Gli , a downstream component of the Hh pathway , we show here that Smo functions as the signaling component of the Shh receptor , and that this activity can be blocked by Ptc . ^^^ The inhibition of Smo by Ptc can be relieved by the addition of Shh . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Lingual expression of the signaling molecule Sonic hedgehog ( Shh ) , its receptor Patched ( Ptc ) , and the Shh activated transcription factor Gli 1 were assayed by using in situ hybridization . ^^^ Ptc and Gli 1 expression follow a pattern similar to that of Shh . ^^^ Compared with Shh , Ptc is expressed in larger regions surrounding the central papillary cells and also in the mesenchyme underlying Shh expressing epithelium . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Expression of ptc and gli genes in talpid 3 suggests bifurcation in Shh pathway . talpid 3 is an embryonic lethal chicken mutation in a molecularly un characterised autosomal gene . ^^^ Here we examine expression of patched ( ptc ) , which encodes a component of the Shh receptor , and is probably itself a direct target of Shh signalling , to establish whether talpid 3 acts in the Shh pathway . ^^^ We also describe genetic mapping of gli 1 , ptc , shh and smoothened in chickens and confirm by co segregation analysis that none of these genes correspond to talpid3 . . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Overlapping and non overlapping Ptch 2 expression with Shh during mouse embryogenesis . ^^^ In the developing tooth , hair and whisker , Shh and Ptch 2 are co expressed in the epithelium while Ptch is strongly expressed in the mesenchymal cells . ^^^ In early mouse embryos , Ptch and Ptch 2 were found to be co expressed in regions adjacent to Shh expressing cells in the developing CNS . ^^^ Similar to other epidermal structures , Shh and Ptch 2 also show overlapping expression in the developing nasal gland and eyelids . ^^^ Thus , during mouse development , Ptch 2 is expressed in both Shh producing and nonproducing cells . . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We have used the mouse developing tooth germ as a model system to explore the transmission of Sonic hedgehog ( Shh ) signal in the induction of Patched ( Ptc ) . ^^^ In the early developing molar tooth germ , Shh is expressed in the dental epithelium , and the transcripts of Shh downstream target genes Ptc and Gli 1 are expressed in dental epithelium as well as adjacent mesenchymal tissue . ^^^ In wild type E11 . 0 molar tooth mesenchyme SHH soaked beads induced the expression of Ptc and Gli 1 . ^^^ However , in Msx 1 mutant dental mesenchyme SHH soaked beads were able to induce Gli 1 but failed to induce Ptc expression , indicating a requirement for Msx 1 in the induction of Ptc by SHH . ^^^ We conclude that in the context of the tooth germ Msx 1 is a component of the Shh signaling pathway that leads to Ptc induction . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The following findings suggest that Sonic hedgehog ( Shh ) is one of the signals . ( 1 ) RGCs express both Shh mRNA and protein , whereas the optic nerve contains the protein but not the mRNA . ( 2 ) Astrocytes and their precursors in the developing optic nerve express the Hedgehog ( Hh ) receptor gene Patched ( Ptc ) , suggesting that they are being signalled by an Hh protein . ( 3 ) Ptc expression in the nerve is greatly decreased by either nerve transection or by treatment with neutralizing anti Shh antibodies , suggesting that it depends on axon derived Shh . ( 4 ) Astrocyte proliferation in the developing nerve is reduced by treatment with anti Shh antibodies , suggesting that Shh normally helps stimulate this proliferation . . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Overexpression of ptc 1 inhibits induction of Shh target genes and prevents normal patterning in the neural tube . ^^^ We find that excess Ptc is sufficient to inhibit expression of Gli 1 and ptc 1 , suggesting that Sonic hedgehog ( Shh ) can not signal effectively . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Ptc , Gli 1 , Bmp 2 , Hoxd 13 , and Fgf 4 are expressed throughout the anteroposterior axis of the mutant limb bud , despite normal Shh expression . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| PCs are thought to provide trophic support for granule neurons [ 2 ] [ 3 ] and to stimulate the proliferation of cells in the EGL [ 4 ] , but the signalling molecules that mediate these cell cell interactions have not been identified . 1 show here that PCs in the developing mouse cerebellum express the gene encoding the morphogen Sonic hedgehog ( Shh ) and that dividing cells in the EGL express Patched ( Ptc ) and Gli 1 , two target genes of which expression is upregulated in response to Hedgehog signalling ( see [ 5 ] and references therein ) . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Expression of BMP 7 , shh , and ptc were uneffected by RET Ig treatment , implying that these genes are regulated independently of ret . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The patched / hedgehog / smoothened signalling pathway in human breast cancer : no evidence for H133Y SHH , PTCH and SMO mutations . ^^^ A substantial proportion of breast carcinomas has recently been suggested to contain missense mutations in the human patched ( PTCH ) and sonic hedgehog ( SHH ) homologues . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Shh might exert its biological functions through binding to patched ( Ptc ) associated with smoothened ( Smo ) , leading to downstream activation of target genes such as the transcription factor Gli 1 . ^^^ We have performed a detailed localization of cells expressing transcripts of Shh , Ptc , Smo and Gli 1 in brain and spinal cord of the adult rat as well as in the developing cerebellum . ^^^ Ptc positive cells were frequently observed in brain areas devoid of any Shh transcripts , except in the median eminence or the facial nucleus , suggesting local Shh signalling . ^^^ The presence of Shh , Ptc and Smo transcripts in hypothalamic areas may indicate a role of Shh signalling in the modulation of neuroendocrine functions . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We show that the two putative receptors of the Shh ligand , Ptc and Ptch 2 , localise in different cells , suggesting Shh may function in different ways as an epithelial and mesenchymal signal . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Transcripts for the putative Shh receptor genes patched ( Ptc ) and smoothened ( Smo ) are expressed by embryonic , postnatal , and adult progenitor cells , suggesting that Shh can act directly on these cells . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Sonic hedgehog ( Shh ) , one of the vertebrate homologs of Hh , controls patterning and growth of the limb but the early embryonic lethality of ptc 1 ( ) ( / ) ( ) mice obscures the roles of ptc 1 in later stages of development . ^^^ The polydactyly was preceded by unexpected anterior limb bud transcription of Shh , so one function of ptc 1 is to repress Shh expression in the anterior limb bud . . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We favor the alternative , that Shh N functions primarily as a ligand for the putative receptor Patched ( Ptc ) . ^^^ This possibility is supported by new evidence for direct binding of Shh N to Ptc and by a strong correlation between the affinity of Ptc binding and the signaling potency of Shh N protein variants carrying alterations of conserved residues in a particular region of the protein surface . ^^^ These results together suggest that direct Shh N binding to Ptc is a critical event in transduction of the Shh N signal . . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| In basal cell nevus syndrome ( BCNS ) patients , mutations of a gene , patched ( ptc ) , which encodes a putative signal transducer of sonic hedgehog protein ( SHH ) , were found and are thought to be one of the major causes of BCNS . ^^^ The SHH signaling pathway is an important developmental pathway , and ptc protein ( PTC ) is a suppressive component serving as a receptor for the secreted SHH . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We also explored time dependency and range of Shh signalling by examining ptc expression . ^^^ We show that high level ptc expression is induced rapidly when either Shh beads or polarising regions are grafted to a host limb . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Using samples from a population based birth defects registry in California , we performed a mutational analysis of the known HPE genes Sonic Hedgehog ( SHH ) , ZIC 2 , and SIX 3 , in addition to two HPE candidate genes , TG interacting factor ( TGIF ) , and Patched ( PTC ) , on a group of sporadic HPE patients . ^^^ No sequence changes were detected in SHH , ZIC 2 , and PTC . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We demonstrate co localization of the Patched 1 ( Ptc 1 ) receptor and its ligand sonic hedgehog ( Shh ) in lysosomes suggests an intracellular sorting mechanism for this receptor and its ligand . ^^^ Treatment of murine brain primary cultures and a human teratoma cell line with the N terminal activated form of Shh ( ShhNT ) , a Ptc 1 Shh complex was observed in lysosomes . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Sonic hedgehog ( Shh ) and Patched ( Ptc ) expression appeared unaffected in the transgenic limb buds , suggesting that the BMPR IB mediated signaling pathway is downstream from Shh . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Purified protein was assayed for biological activity and found to activate the transcription of the Patched genes ( Ptc 1 and Ptc 2 ) encoding receptors for SHH . . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The ontogeny of expression of the mesodermal markers shh , ptc , bmp 2 , and hoxd 12 and 13 , as well as the ectodermal markers wnt7a , fgf 4 , fgf 8 , cx 43 , and p 21 occurred normally in day 9 . 5 teratogen exposed limb buds . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Analysis of PTCH / SMO / SHH pathway genes in medulloblastoma . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Syndrome related disorders have been attributed to alterations of PTCH gene , which plays an important role in Shh signalling pathway . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| By using a murine retrovirus to ectopically express Wnt 7b in presumptive dental ectoderm in mandibular arch explants , we show that Shh expression in the ectoderm and Ptc expression in the underlying ectomesenchyme are down regulated , and tooth development is subsequently arrested . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Defects in a developmental signaling pathway involving mammalian homologues of the Drosophila segment polarity gene , patched ( ptc ) and its ligand , sonic hedgehog ( shh ) , contribute to tumor formation in several tissues . ^^^ High levels of glil mRNA and protein were detected in the tumors , suggesting that the shh / ptc pathway was activated despite the persistence of ptc expression . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Constitutional hemizygous inactivation of PTCH , the Shh signaling pathway gene that moderates the signal , manifests itself as nevoid basal cell carcinoma syndrome or Gorlin syndrome , a condition variably characterized by a number of developmental disorders and malformations , and by predisposition to some malignancies , basal cell carcinoma in particular . ^^^ Suggestive temporal distribution of Shh signaling , recently observed during tooth development , lead us to investigate PTCH association with dentigerous cysts , the other major noninflammatory cyst of odontogenic origin . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Dorsally expressed Shh signals induce ectopic transcription of its receptor Ptc 1 in the midbrain and the hindbrain . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We have tested whether this activity of cyclopamine is related to disruption of cellular cholesterol transport and putative secondary effects on the Shh receptor , Patched ( Ptc ) . ^^^ However , compounds that block cholesterol transport by affecting the vesicular trafficking of the Niemann Pick C 1 protein ( NPC 1 ) , which is structurally similar to Ptc , are weak Shh antagonists . ^^^ Rather than supporting a direct link between cholesterol homeostasis and Shh signaling , our findings suggest that the functions of both NPC 1 and Ptc involve a common vesicular transport pathway . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Shh internalization is blocked by a monoclonal antibody whose epitope overlaps the Ptc binding site of Shh . ^^^ These findings suggest that Shh internalization is mediated by Ptc 1 and may be linked to signaling . ^^^ Concordantly , transfection of mammalian cell lines with a Ptc 1 cDNA confers the ability to internalize multiple forms of Shh , including transmembrane anchored Shh , by a dynamin dependent process . . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The similarity of the Shh receptor , Patched ( Ptc ) , to the Niemann Pick Cl protein , which is involved in the vesicular trafficking of cholesterol , provides insight into the role of cholesterol and the action of compounds like cyclopamine . . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Furthermore , addition of the ptc 1 ligand , sonic hedgehog ( shh ) , disrupts this interaction and allows cyclin B 1 to localize to the nucleus . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We further demonstrate that the availability of s ShhNp is regulated by two functional antagonists of the Shh pathway , Patched ( Ptc ) and Hedgehog interacting protein ( Hip ) . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We show that Smo acts epistatic to Ptc 1 to mediate Shh and Ihh signaling in the early mouse embryo . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Shh and Ptc are associated with taste bud maintenance in the adult mouse . ^^^ We found that the receptor for Sonic hedgehog ( Shh ) , Patched 1 ( Ptc ) , was expressed around taste buds where cells were proliferating , and that Shh was expressed within basal cells of taste buds . ^^^ Denervation caused the loss of Shh and Ptc expression before the degeneration of taste buds . . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The abnormalities are associated with congenital or sporadic genetic alteration affecting function of different components of the HH signaling pathway , including SHH , PTCH , SMOH and GLI proteins . . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Here we tested the genetic interaction between Sil and the Shh pathway by generating and analyzing embryos carrying mutations in both Sil and Patched ( Ptch ) , a Shh receptor that normally inhibits the signaling pathway in the absence of ligand and when mutated leads to constitutive activation of the pathway . ^^^ We find that Sil ( / ) Ptch ( / ) embryos do not activate the Shh pathway and instead have a phenotype indistinguishable from Sil ( / ) embryos , in which there is a loss of activity of Shh . ^^^ These results provide genetic evidence that Sil is an essential component of the Shh response , acting downstream to Ptch . . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Sonic Hedgehog ( Shh ) and Patched ( Ptc ) were found only in the dorsal tongue epithelium . ^^^ Shh expression was only observed in the suprabasal layers , whereas Ptc was observed in both basal and suprabasal layers . ^^^ Shh and Ptc expression were never detected in the mesenchyme . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Functional analysis by organ culture revealed that Shh could regulate mesenchymally expressed genes , patched 1 ( Ptch 1 ) , bone morphogenetic protein 4 ( Bmp 4 ) , Hoxd 13 and fibroblast growth factor 10 ( Fgf 10 ) , in the anlage : the genital tubercle ( GT ) . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The Patchedl ( Ptc 1 ) protein is a receptor for Sonic hedgehog ( Shh ) , a secreted protein ligand . ^^^ Ptc 1 limits the effects of the Shh signal , so mutations in PTCH may lead to persistent granule cell precursors susceptible to further genetic or environmental events that cause medulloblastoma . ^^^ Ptc 1 limits the effects of the Shh signal , so mutations in PTCH may lead to persistent granule cell precursors susceptible to further genetic or environmental events that cause medulloblastoma . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Shh displays inductive , proliferative , neurotrophic and neuroprotective activities on various neural cells and signals through a receptor complex associating Patched ( Ptc ) and Smoothened ( Smo ) . ^^^ Shh binding to Ptc leads to downstream activation of target genes , such as transcription factors of the Gli family . ^^^ In the ventral neural tube , the distribution of Shh , Ptc and Smo is in agreement with this functional model . ^^^ These observations suggest that in the adult brain , Shh signals through its receptor complex Ptc / Smo , or through Ptc alone . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| They first appear within a region of anterior hypothalamic neuroepithelium that co expresses mRNA encoding SHH , its receptor PTC 1 ( PTCH ) and the transcription factors OLIG 1 , OLIG 2 and SOX 10 . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| It has been postulated that binding of sonic hedgehog protein ( SHH ) to its receptor , patched protein ( PTC ) , releases the inhibitory effect of PTC against smoothened protein ( SMO ) , another protein of the SHH signalling pathway . ^^^ Recently , hedgehog interacting protein ( HIP ) was found to bind to SHH directly and attenuate SHH signalling like PTC , while its expression was induced by SHH signals . ^^^ OBJECTIVES : To examine the expression patterns of HIP , SHH and PTC gene mRNA by human BCCs , in comparison with those by normal human skin and various skin tumours . ^^^ CONCLUSIONS : These results indicate that both HIP and PTC gene expression are specifically involved in the development of BCCs , and that the production of HIP is linked with the expression of the PTC gene but not the SHH gene . . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Shh was similarly expressed in the floor plate of the mutant hindbrain , while the expressions of Ptc 1 , Gli 1 and Gli 2 were altered only in the progenitor domains for the motoneurones . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We quantitated the expression levels of Shh and its receptor genes , Patched ( Ptc ) and Patched 2 ( Ptch 2 ) , in two distinct experimental systems in which the development of hair follicles was suppressed . ^^^ Shh , Ptc , and Ptch 2 were induced about six to tenfold in normal embryonic hair germs in vivo as well as in developing skin tissue maintained in organ culture . ^^^ Expression of Shh , Ptc and Ptch 2 was induced in the Tabby embryos at 16 . 5 days postcoitus , indicating that Shh signaling may be involved in the formation not only of the well studied guard hair but also of the awl hair . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| This results in down regulation of Ptc , a principle target of Shh signaling . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Fine gene mapping in this study indicated that mes is tightly linked to patched ( ptc ) that encodes a transmembrane receptor protein for Shh . ^^^ Since mes homozygous embryos exhibit normal spinal cord development as compared with ptc ( ) homozygotes , which die around 10 dpc with severe neural tube defects , the C terminal cytoplasmic domain lost in mes mutation is dispensable for inhibition of Shh signaling in early embryogenesis . ^^^ These findings indicate that Ptc is a negative regulator of body weight and ectopic activation of Shh signaling in the anterior mesenchyme of the limb buds , and that the C terminal cytoplasmic domain of Ptc is involved in its repressive action . . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Here we show that Shh and its receptor , Ptc 1 , are expressed in the adult rat basal forebrain , and that Ptc 1 is expressed specifically by cholinergic neurons . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Absence of WNT5a activity in the mutant lungs leads to increased expression of Fgf 10 , Bmp 4 , Shh , and its receptor Ptc , raising the possibility that WNT5a , FGF 10 , BMP 4 , and SHH signaling pathways are functionally interactive . . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| PATCHED 1 ( PTCH ) , the receptor for SHH , normally acts to repress SHH signaling . ^^^ This repression is relieved when SHH binds to PTCH . ^^^ We predict that by enhancing the repressive activity of PTCH on the SHH pathway , these mutations cause decreased SHH signaling , and HPE results . ^^^ The mutations could affect the ability of PTCH to bind SHH or perturb the intracellular interactions of PTCH with other proteins involved in SHH signaling . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| When SSC cells were transduced with Ptc virus , colony forming activity in soft agar was drastically reduced and these cells recovered anchorage independent growth when Sonic hedgehog ( Shh ) , the ligand of Patched ( Ptc ) , was added into the soft agar culture . ^^^ Cyclopamine , a specific inhibitor of the Shh / Ptc / Smo signaling pathway , efficiently suppressed anchorage independent growth of A 431 and KA cells . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We also find that Ta mutants lack completely the placodes of the first developing tylotrich hairs , and that they do not show patterned expression of placodal genes , including Bmp 4 , Lef 1 , Shh , Ptch and Edar , and the genes for beta catenin and activin A . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Morphological changes were accompanied by an expansion , followed by a reduction , in domains of shh expression and a rapid abolition of ptc 1 expression . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Individuals with germline mutations of the SHH receptor gene PTCH are at high risk of developmental anomalies and of basal cell carcinomas , medulloblastomas and other cancers ( a pattern consistent with nevoid basal cell carcinoma syndrome , NBCCS ) . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| In heterozygous ptc 1 cells , ptc 1 lacZ was expressed at low levels but could be induced by Sonic Hedgehog ( Shh ) and Gli 1 . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Therefore , CUSP appears to be present , unmutated , and yet frequently undetectable by immunofluorescence in cutaneous lesions in both humans and mice that are associated with SHH pathway dysregulation ( BCCs , BCNS , and nevus sebaceous ) . . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : Sonic hedgehog ( Shh ) signal transduction involves the ligand binding Patched 1 ( Ptc 1 ) protein and a signaling component , Smoothened ( Smo ) . ^^^ A select group of compounds inhibits both Shh signaling , regulated by Ptc 1 , and late endosomal lipid sorting , regulated by the Ptc related Niemann Pick C 1 ( NPC 1 ) protein . ^^^ Ptc 1 and Smo colocalize extensively in the absence of ligand and are internalized together after ligand binding , but Smo becomes segregated from Ptc1 / Shh complexes destined for lysosomal degradation . ^^^ Ligand induced segregation allows Smo to signal independently of Ptc 1 after becoming sorted from Ptc1 / Shh complexes in the late endocytic pathway . . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| This is accompanied by disruption of the expression of genes ( Shh , Gli 1 , Gli 2 , Gli 3 , and Ptch ) associated with SHH signalling in the limb bud mesenchyme , the down regulation of Bmp 4 in the apical ectoderm , the absence of Alx 3 , Alx 4 , Pax 1 , and Pax 3 activity in the mesenchyme , and a reduced potency of the limb bud tissues to differentiate into osteogenic and myogenic tissues . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The sonic hedgehog ( SHH ) patched ( PTCH ) pathway functions in normal embryonic development of the brain , musculoskeletal system , and hair follicles , and in normal post natal control of hair follicles . ^^^ Based on the knowledge that generalized , prolonged PTCH expression can inhibit the effects of SHH signaling , we tested the hypothesis that localized transient overexpression of PTCH would inhibit the phenotype of SHH induced accelerated growth of hair follicles . ^^^ Thus , PTCH expression mediated by gene transfer can modulate the SHH signaling pathway in the adult mammal and may serve as a starting point for therapies relevant to clinical conditions resulting from dysregulation of this pathway as well as for strategies to suppress normal SHH dependent processes , such as hair growth . . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Furthermore , functional assays demonstrated that whereas all PTCH 1 isoforms can inhibit the activity of SHH , only the PTCH1B isoform is capable of fully inhibiting Smoh activity . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Sonic Hedgehog ( Shh ) is a secreted morphogen that directs patterning and cellular differentiation through binding to its receptor Patched ( Ptc ) . ^^^ No reduction of Ptc 1 transcripts was observed in Shh null mammary tissues . ^^^ Our results demonstrate that neither Shh nor Ihh is required for mammary gland morphogenesis and functional differentiation , suggesting that the two members of the Hedgehog family may have redundant function in activating the Ptc 1 signaling pathway during mammary gland development . . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The gene for the Shh receptor , Ptc 1 , is expressed in the UGM , as are the members of the Gli gene family of transcriptional regulators ( Gli 1 , Gli 2 , and Gli 3 ) . ^^^ A strong dependence of Gli 1 ( and Ptc 1 ) expression on Shh signaling is demonstrated by induction of expression in both the intact urogenital sinus and the isolated UGM by exogenous SHH peptide . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Patched ( Ptc ) is a transmembrane receptor for sonic hedgehog ( Shh ) and functionally associated with another transmembrane protein , smoothened ( Smo ) . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We have performed a time course analysis of the expression of Sonichedgehog ( shh ) and patched 1 ( ptc 1 ) in response to exogenous retinoic acid ( RA ) application to get some insight into the mechanism ( s ) underlying the formation of a mirror image duplication of shh and ptc 1 domains of expression in the pectoral fin buds of zebrafish . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Prior to the ectopic induction of Shh , the expression domains of genes downstream from Shh , namely dHAND , Gli 1 , Ptc and Gre , which are normally expressed in posterior mesenchyme of limb buds , expanded anteriorly on the lx hindlimb buds . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We have investigated the expression of Hip during early tooth development and found it not to be localized in cells immediately adjacent to Shh expressing cells , but rather at a distance , separated by cells expressing Ptc 1 . ^^^ A role for Hip might be to prevent the spread of excess Shh ligand beyond an immediate Ptc 1 induced zone in odontogenic mesenchyme . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Shh signals through interaction with the tumour suppressor Patched ( Ptc ) . ^^^ The study described here shows that injection of aminoterminal myristoylated Shh ( myrShhN ) into the adult rat striatum robustly increases the levels of Ptc transcripts in selective brain areas including the subventricular zone ( SVZ ) . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| To test this hypothesis , Shh , BMP 4 , Ptc , and Hoxa 10 localization and function were examined in Sprague Dawley rat penes by means of quantitative reverse transcription polymerase chain reaction , in situ hybridization , immunohistochemistry , and Western blotting . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The mandibular cysts were immunohistochemically investigated using anti ptc , shh , and smo antibodies . ^^^ Immunohistochemical examination showed sonic hedgehog ( shh ) protein mainly in cyst lining epithelium , and ptc and smoothened ( smo ) proteins in cyst lining epithelium , and surrounding fibrous connective tissue . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| To determine whether Gli 1 contributes to the defects seen when the Shh pathway is inappropriately activated and Gli 1 transcription is induced , Gli 1 ; Ptc double mutants were generated . ^^^ We show that Gli 1 is not required for the ectopic activation of the Shh signaling pathway or to the early embryonic lethal phenotype in Ptc null mutants . ^^^ Of significance , we found instead that Gli 2 is required for mediating some of the inappropriate Shh signaling in Ptc mutants . ^^^ Our studies demonstrate that , in mammals , Gli 1 is not required for Shh signaling and that Gli 2 mediates inappropriate activation of the pathway due to loss of the negative regulator Ptc . . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| In this study , we demonstrate that Shh and its receptor Patched ( Ptc ) are expressed on resting and activated human peripheral CD 4 ( + ) T cells . ^^^ In approximately one half of the randomly selected , anonymous blood donors tested , exposure of anti CD3 / 28 Ab activated CD 4 ( + ) T cells to the biologically active N terminal Shh peptide increased the transcription of ptc , thereby demonstrating that Shh signaling had occurred . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The authors aimed to study the temporal and spatial pattern of expression of Shh and its receptor Ptc 1 during the development of the anterior foregut and to test the hypothesis that the Shh expression pattern is disturbed during the development of oesophageal atresia ( OA ) and tracheo oesophageal fistula ( TOF ) in Adriamycin treated mouse embryos . ^^^ METHODS : Saline and Adriamycin treated ( 4 mg / kg ) CBA / Ca embryos were harvested between embryonic days ( E ) 10 . 5 and 12 . 5 , and Shh and Ptc 1 expression was studied by whole mount and section in situ hybridisation using digoxygenin labelled riboprobes . ^^^ Ptc 1 was expressed in the mesoderm adjacent to Shh expressing endoderm at both stages . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Ptc protein had a similar distribution to Shh , although the immunoproduct was more diffuse . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The Shh receptors Ptc 1 ( Patched 1 ) and Ptc 2 were found to be expressed in prostatic stromal cells adjacent to the epithelium , where Shh itself was produced . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Disorders of the sonic hedgehog signaling network are discussed next , including holoprosencephaly and the nevoid basal cell carcinoma syndrome , the former being caused by sonic hedgehog ( SHH ) mutations and the latter being caused by patched mutations ( PTCH ) . . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| In addition , Shh upregulates several mesenchymal cell markers , including its target gene Patched ( Ptc ) , intercellular signaling genes Bone Morphogenetic Protein 4 ( Bmp 4 ) and Noggin ( Nog ) , and smooth muscle actin and myosin . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : Mutations of the patched ( Ptc ) gene , a developmental regulator implicated in the signalling pathway via sonic hedgehog ( Shh ) and smoothened ( Smo ) , play an essential pathogenic role in the development of basal cell carcinomas ( BCCs ) . ^^^ We previously reported the upregulation of Shh signal transducers , including Ptc , Smo and hedgehog interacting protein , in BCCs . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| It differs from other polydactylous mutants in showing normal Shh expression , but polarizing activity ( shown by mouse chick grafting experiments ) and hedgehog signalling activity ( shown by expression of Ptc 1 ) are present throughout the distal mesenchyme . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Furthermore , these conditions resulted in transcriptional activation of smoothened ( smo ) , patched ( ptc ) and gli 1 ; Smo , Ptc and Gli 1 , as well as cholesterol , are components of the Sonic hedgehog ( Shh ) signalling pathway , which directs pattern formation , diversification and tumourigenesis in mammalian cells . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Mutants lacking Patched 1 ( Ptc 1 ) , the putative receptor of Shh , were used to analyze Gli functions . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Expression of Shh , Ptc 1 , Ptc 2 mRNA in the cap stage of mouse molar ] . ^^^ OBJECTIVE : To investigate the expression of Shh and its receptors Ptc 1 and Ptc 2 mRNA in the cap stage of mouse molar and discuss its role in early tooth morphogenesis . ^^^ The expression pattern of Shh , Ptc 1 , and Ptc 2 mRNA was analysed by in situ hybridization . ^^^ Shh , Ptc 1 , and Ptc 2 mRNA were strongly expressed in outer dental epithelium , inner dental epithelium , stellate reticulum and the enamel knot . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| In addition , the Ptc 1 receptor is activated in interstitial mesenchymal cells within the ischemic area , indicating that these cells respond to Shh and that the Shh pathway is functional . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We show that Patched ( Ptc ) induces apoptotic cell death unless its ligand Shh is present to block the signal . ^^^ Moreover , the blockade of Ptc induced cell death partly rescues the chick spinal cord defect provoked by Shh deprivation . ^^^ Thus , the proapoptotic activity of unbound Ptc and the positive effect of Shh bound Ptc on cell differentiation probably cooperate to achieve the appropriate spinal cord development . . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Accompanying overexpression of beta catenin is up regulation of Sonic hedgehog ( SHH ) and its receptor , Patched ( PTCH / Ptch ) . ^^^ In DeltaNLef 1 tumors Ptch mRNA is up regulated in the absence of SHH . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The secreted protein Sonic hedgehog ( Shh ) and its transmembrane receptor Patched ( Ptc ) control a major signal transduction pathway in early vertebrate limb development . ^^^ Ligand bound Ptc removes the block and leads to further expression of ptc , which in turn restricts the range of Shh transport . ^^^ We develop a model to study the effects of two forms of Shh used experimentally and propose a mechanism for Shh signal transduction based on a two state model for the Ptc Smo interaction . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We found by in situ hybridization that the SHH autocrine receptor Ptch 2 is indeed expressed in dental epithelium whereas the paracrine receptor Ptc is expressed in mesenchyme . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The pathways we focus on in this review are : ( 1 ) P 16 ( INK4A ) CDK4 / 6 RB ; ( 2 ) P 14 ( ARF ) HDM 2 P53 ; ( 3 ) Sonic hedgehog ( SHH ) / GLI ; ( 4 ) WNT / beta catenin ; and ( 5 ) Bone Morphogenetic Protein ( BMP ) / SMAD . 70 80 % of XP skin cancers exhibit one or several mutations in the P 53 , PTCH 1 , SMO or CDKN2A genes , the type and frequency of mutated genes being different between squamous cell ( SCCs ) and basal cell carcinomas ( BCCs ) . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Mutations of the Shh receptor PATCHED ( PTCH ) are associated with medulloblastomas , which have not been found to have loss of PTCH heterozygosity . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Basal cell carcinomas are characterized by aberrant activation of Sonic Hedgehog ( SHH ) signaling due to mutations in the PTCH or SMOH genes . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We have demonstrated that Shh and Ptc expression correlates with growth and development of the prostate and that their expression is not regulated by androgens in the VP . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| In this study we investigated the expression of key factors in the Shh pathway , namely Shh and its receptor Patched ( Ptc ) , in normal and pathologic stomach mucosa . ^^^ Expression of Shh and Ptc was analyzed by immunohistochemistry . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| To determine whether this signaling system is important in vivo for regulating retinal progenitor proliferation , we analyzed mice with a single functional allele of the Shh receptor patched ( ptc ) . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The roles of crucial factors identified from relevant animal model systems , including BMP 4 and SHH , and the likely events perturbed by key genes pinpointed in human studies [ such as PVRL 1 , IRF6p63 , MID 1 , MSX 1 , and PTCH 1 ] are discussed in this light . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We also demonstrate linked overexpression of BMI 1 and patched ( PTCH ) , suggestive of SHH pathway activation , in a substantial fraction of primary human medulloblastomas . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| To address this question , we first determined the spatiotemporal distribution of Shh ; two transmembrane proteins , patched 1 ( Ptc ) and Smoothened ( Smo ) , which act as a negative or a positive regulator of the Shh signal , respectively ; and the Gli 3 transcription factor , which is downstream of the Shh signal . ^^^ The epithelial localization of Shh , Ptc , Smo , and Gli 3 suggests that Shh signaling may act within the epithelium in a juxtacrine manner . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| PTCH 2 promoter regulation assays demonstrated that only one of the PTCH 2 variants could inhibit the activity of SHH N , whereas none was capable of inhibiting the activated form of SMO ( SMO M 2 ) and this contrasts with PTCH 1 . ^^^ Using Ptch 1 / mouse cells , it was shown that the PTCH 2 variants and PTCH 1 differentially act to reconstitute not only the SHH but also the Desert HH dependent transcriptional response . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : To clarify the roles of Sonic hedgehog ( SHH ) signal transduction in oncogenesis and cytodifferentiation of odontogenic tumors , expression of SHH , Patched ( PTC ) , Smoothened ( SMO ) , and GLI 1 was analyzed in ameloblastomas as well as in tooth germs . ^^^ METHODS : Tissue specimens of 9 tooth germs , 36 benign ameloblastomas , and 1 malignant ameloblastoma were examined by reverse transcriptase polymerase chain reaction ( RT PCR ) and immunohistochemistry for the expression of SHH , PTC , SMO , and GLI 1 . ^^^ RESULTS : Expression of SHH , PTC , SMO , and GLI 1 mRNA was detected in all tooth germ and ameloblastoma samples . ^^^ Immunohistochemical reactivity for SHH , PTC , SMO , and GLI 1 was detected in both normal and neoplastic odontogenic tissues . ^^^ Expression of SHH , PTC , and GLI 1 was more evident in epithelial cells than in mesenchymal cells , whereas SMO reactivity was marked in both epithelial and mesenchymal components in tooth germs and ameloblastomas . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We show that at these stages in the murine mandibular arch in the absence of epithelium , the Shh targets Ptc 1 and Gli 1 are upregulated in diastema mesenchyme , an edentulous region between the sites of molar and incisor tooth formation . ^^^ Although Shh signalling has no effect upon Gas 1 expression in mandibular arch mesenchyme , overexpression of Gas 1 results in downregulation of ectopic Ptc 1 . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Sonic hedgehog ( Shh ) binds to its receptor patched ( PTCH ) , leading to the activation and repression of target genes via the GLI family of zinc finger transcription factors . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Shh , the secreted signal molecule , patched ( Ptc ) , its membrane receptor , and Gli 1 , a downstream transcription factor , were detected at the gene level with semiquantitative reverse transcriptase polymerase chain reaction ( RT PCR ) and at the protein level with Western blot analysis . ^^^ EDL did not alter epididymal segmentation , but Shh , Ptc , and Gli 1 expression was significantly altered at specific times after the ligation . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Through genetic combinations with null alleles of patched 1 ( Ptch 1 ) , sonic hedgehog ( Shh ) and Indian hedgehog ( Ihh ) , we demonstrate that Disp 1 genetically interacts with Hh signaling components . ^^^ Conversely , increasing available Shh ligand by decreasing Ptch 1 dosage leads to the restoration of ventral cell types in Disp 1 ( Delta2 / Delta2 ) mutants . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| METHODS : Immunofluorescent staining and Western blot analysis were used to detect Shh , patched 1 ( Ptc 1 ) receptors , and Gli transcription factors in corneal epithelium of Wistar rats ( n = 44 ) at various intervals after an epithelial defect . ^^^ RESULTS : Uninjured rat corneal epithelium was not labeled by anti Shh antibody , but weakly positive for Ptc 1 . ^^^ Basal cells of limbal and conjunctival epithelia were labeled by antibodies against Shh and Ptc 1 . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| METHODS : Inhibition of Hh signaling by HIP was assayed by measuring the induction of Ptc 1 mRNA in TM 3 cells treated with conditioned medium containing Sonic hedgehog ( Shh ) . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The Patched ( PTC ) gene is responsible for basal cell nevus syndrome ( BCNS ) accompanied by multiple odontogenic keratocysts ( OKCs ) , and its product plays a role in the Sonic hedgehog ( SHH ) signaling pathway involving smoothened ( SMO ) and GLI 1 . ^^^ To clarify the role of SHH signaling in OKCs , the expression of SHH , PTC , SMO , and GLI 1 and mutations of PTC were examined in 18 sporadic , 4 BCNS associated OKCs and 7 control gingivae . ^^^ PTC gene mutations and expression of SHH , PTC , SMO , and GLI 1 in odontogenic keratocysts . ^^^ SHH , PTC , SMO , and GLI 1 were detected in all OKC and gingiva samples by reverse transcriptase polymerase chain reaction ( RT PCR ) . ^^^ Immunoreactivity for SHH and GLI 1 was markedly higher in epithelial components than in subepithelial cells , while immunoreactivity for PTC and SMO was similar in epithelial components and subepithelial cells in OKCs . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Herein , we examined Sonic hedgehog ( Shh ) patched ( ptc ) gli in the developing rat prostate gland , its role in branching morphogenesis , and the effects of neonatal estrogens on its expression and localization to determine whether a disturbance in this signaling pathway is involved in mediating the estrogenized phenotype . ^^^ Shh was expressed in epithelial cells at the distal tips of elongating ducts in discreet , heterogeneous foci , while ptc and gli 1 3 were expressed in the adjacent mesenchymal cells in the developing gland . ^^^ Neonatal exposure to high dose estradiol suppressed Shh , ptc , gli 1 , and gli 3 expressions and concomitantly blocked ductal branching in the dorsal and lateral prostate lobes specifically . ^^^ In contrast , ventral lobe branching and Shh ptc gli expression were minimally affected by estrogen exposure . ^^^ Organ culture studies with lateral prostates confirmed that estradiol suppressed Shh ptc gli expression directly at the prostatic level . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The expression of SHH receptor , Patched 1 ( Ptc 1 ) , was greatly increased in all cartilage , as well as the expression of parathyroid hormone related protein ( PTHrP ) at the articular surface ; while the expression of Indian Hedgehog ( Ihh ) , another member of Hh family that controls the rate of chondrocyte maturation , was greatly reduced and restricted to the displaced chondrocyte columns . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Suppression of the Shh pathway using a small molecule inhibitor eliminates medulloblastoma in Ptc 1 ( + / ) p 53 ( / ) mice . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Accordingly , GLI 1 3 and PTCH 1 mRNAs were expressed at moderate levels , and sonic hedgehog ( SHH ) mRNA expression was low to undetectable . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Signals of Hedgehog family proteins ( SHH , IHH and DHH ) are transduced through Patched family receptors ( PTCH 1 and PTCH 2 ) and Smoothened ( SMO ) to GLI family transcription factors ( GLI 1 , GLI 2 and GLI 3 ) . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We show that Shh expression domains are lost from the talpid ( 3 ) head in hindbrain , midbrain , zona limitans intrathalamica , and stomodeal ectoderm and that direct targets of Hedgehog signaling , Ptc 1 , Ptc 2 , and Gli 1 , are also absent even in areas associated with primary Shh expression . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| In the cerebellum from IFN gamma expressing but not age matched non IFN gamma expressing mice , the level of Shh and Gli 1 but not Patched ( Ptch ) 1 RNA was increased as was the 19 kDa signaling product of the Shh precursor protein . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Now we have immunolocalized the Shh protein and the Patched receptor protein ( Ptc ) , and have tested potential roles for Shh in formation of the tongue , emergence of papilla placodes , development of papilla number and size , and maintenance of papillae after morphogenesis is advanced . ^^^ Shh and Ptc proteins are diffuse in prelingual tissue and early tongue swellings , and are progressively restricted to papilla placodes and then to regions of developing papillae . ^^^ Ptc encircles the dense Shh immunoproduct in papillae at various stages . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Constitutive activation of the shh ptc 1 pathway by a patched 1 mutation identified in BCC . ^^^ The ptc 1 Q688X mutant enhances Gli 1 activity , a downstream reporter of sonic hedgehog ( shh ) ptc 1 signaling , independent of shh stimulation . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Binding of Sonic Hedgehog ( Shh ) to Patched ( Ptc ) relieves the latter ' s tonic inhibition of Smoothened ( Smo ) , a receptor that spans the cell membrane seven times . ^^^ Ptc inhibits association of beta arrestin 2 with Smo , and this inhibition is relieved in cells treated with Shh . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Sonic hedgehog ( SHH ) , Desert hedgehog ( DHH ) and Indian hedgehog ( IHH ) bind to Patched family receptors ( PTCH 1 and PTCH 2 ) to transduce signals to GLI 1 , GLI 2 and GLI 3 . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Shh and its mediators Ptc 1 , Ptc 2 , and Gli 1 were down regulated only in the lower but not the upper molars of Runx 2 and Runx2 / Runx3 knockouts . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We have recently shown that developmental expression of Shh ptc gli is downregulated in the dorsolateral prostate following estrogenization , and this is responsible , in part , for branching deficits observed in that prostatic region specifically . ^^^ Fgf 10 and FgfR2iiib localize to the distal signaling center of elongating and branching ducts in separate prostate lobes where they regulate the expression of multiple morphoregulatory genes including Shh , ptc , Bmp 7 , Bmp 4 , Hoxb 13 , and Nkx3 . 1 . ^^^ Similar to Shh ptc gli , neonatal estrogen exposure downregulates Fgf 10 , FgfR2iiib , and Bmp 7 expression in the dorsolateral prostate while ventral lobe expression of these genes is unaffected . ^^^ Together , these studies demonstrate that alterations in Fgf 10 signaling are a proximate cause of Shh ptc gli and Bmp 7 downregulation that together result in branching inhibition of the dorsolateral prostate following neonatal estrogen exposure . . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| A growing list of diverse antagonists have been identified that restrict Shh signalling in the embryo , however , only Ptc 1 , Gas 1 and Hip 1 have been studied during tooth development . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| PTCH , a 12 pass transmembrane protein , is a receptor for Sonic hedgehog ( Shh ) signaling proteins . ^^^ Shh proteins activate transcription of target genes , including PTCH , via GLI transcription factors . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| In monolayer P 19 ( Shh ) cultures the Shh pathway was functional as shown by the up regulation of Ptc 1 and Gli 1 expression , but no cardiac muscle markers were activated . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Patched 1 ( Ptc 1 ) functions as a receptor for Sonic hedgehog ( Shh ) in a wide range of biological processes . ^^^ Binding of Shh to Ptc 1 results in activation of Smoothened ( Smo ) , which in turn stimulates expression of downstream target genes including Ptc 1 and Gli 1 . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Herein , we quantitatively confirm that expression of Shh , Ptch 1 , and Gli 3 are unaltered by teratogen exposure and demonstrate that sonic hedgehog ( Shh ) translation is unaffected . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The sonic hedgehog ( Shh ) transcript is localized to the cancer tissue , whereas expression of Gli 1 and PTCH 1 is observed both in the cancer and in the surrounding stroma . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Sonic hedgehog ( Shh ) expression is normal , yet Ptch 1 and Gli 1 , two known targets of Hh signaling , are greatly reduced , consistent with loss of Shh signaling . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| During the same developmental period Noggin mRNA is highly expressed throughout the spine , in the developing AF , while ptc protein and SHH mRNA were expressed in the developing nucleus pulposus ( NP ) . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| For example , Shh was not induced in the frontonasal ectoderm , and Ptc and Gli 1 were reduced in both the ectoderm and adjacent mesenchyme . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| However , overexpression of shh does not increase median pituitary placode size nor does it upregulate patched ( ptc ) expression in pituitary precursors during early somitogenesis . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| This effect of Shh was not mediated by Patched ( Ptc ) and Smoothened ( Smo ) , the receptors that mediate effects of Shh in morphogenesis and commissural axon growth toward the floor plate . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Expression of activated EGFR causes pre and postaxial polydactyly , including mirror image type digit duplication , likely due to induction of ectopic expression and / or modulation of genes involved in anterior posterior ( AP ) patterning such as Sonic hedgehog ( Shh ) , dHand , Patched ( Ptc ) , Gli 3 , Hoxd 13 , Hoxd 11 , bone morphogenetic protein 2 ( Bmp 2 ) , Gremlin , and FGF 4 . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Xenotransplants were characterized with histochemistry ( HE , PAS ) , immunohistochemistry ( cytokeratin ( CK ) 7 , CK 8 , CK 18 , CK 19 , CK 20 , vimentin , chromogranin A ( Chr A ) , alpha 1 antichymotrypsin ( alpha 1 chym ) , beta catenin , laminin 5 , pancreatic and duodenal homeobox gene 1 ( pdx 1 ) , sonic hedgehog protein ( shh ) , Patched ( ptc ) ) , Western blotting and real time PCR ( CK 7 , CK 8 , CK 20 , Chr A , pdx 1 , shh , ptc ) . ^^^ Predominantly the CK 7 positive ductal phenotype ( YAPC and DAN G ) was associated with pdx 1 expression , whereas the CK 8 positive solid phenotype was associated with shh / ptc expression on protein and mRNA level . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| While the sonic hedgehog ( Shh ) transcript is localized to the tumor tissue , expression of Gli 1 and PTCH 1 is observed both in the tumor and in the stroma . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The transmembrane receptor Patched ( Ptc ) mediates the action of the diffusing factor Sonic hedgehog ( Shh ) , which is implicated in establishing morphogenetic gradients during embryonic development . ^^^ Here we describe the complementary pattern of Shh and Ptc expression in the rat dorsal vagal motor nucleus and the ventrolateral nucleus tractus solitarius ( vNTS ) , respectively . ^^^ Both inhibiting and bursting effects are blocked by the monoclonal Shh antibody 5E1 and may require the Ptc binding site of ShhN . ^^^ |
|
| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| METHODS : Using immunohistochemistry , we determined the expression of Shh and its receptors Patched 1 ( Ptc 1 ) and Patched 2 ( Ptc 2 ) in 55 human pituitary adenomas compared with the normal pituitary gland . ^^^ RESULTS : Ptc 1 and Ptc 2 were present , whereas Shh was down regulated in pituitary adenomas and completely absent in Cushing tumors . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The receptor Ptc 1 and a regulator of Hh signalling Hhip 1 are expressed in the mesenchyme adjacent to the palatal oral epithelium so that the highest level of transcripts localize to the palatal mesenchyme surrounding the Shh expressing thickened epithelium . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Both levels and distribution of SHH receptor , Ptc were reduced in SpC Wnt5a transgenic lungs and were reciprocally correlated to changes of Fgf 10 in the mesenchyme , suggesting that SHH signaling is decreased by over expression of Wnt5a . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Hh agonist induced hair growth caused no detectable differences in epidermal proliferation , differentiation , or in the endogenous Hh signaling pathway as measured by Gli 1 , Shh , Ptc 1 , and Gli 2 gene expression when compared with a normal hair cycle . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Our results suggest that both acute and chronic ECS enhance Shh signalling in the adult hippocampus , as we observed a robust upregulation of Patched ( Ptc ) mRNA , a component of the Shh receptor complex and a downstream transcriptional target of Shh signalling . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Human SHH , IHH , DHH ( Hedgehog homologs ) , HHAT ( Hedgehog acyltransferase ) , HHIP ( Hedgehog interacting protein ) , DISP 1 , DISP 2 , DISP 3 ( Dispatched homologs ) , PTCH 1 , PTCH 2 ( Patched homologs ) , SMO ( Smoothened homolog ) , KIF 27 , KIF 7 ( Costal 2 homologs ) , STK 36 ( Fused homolog ) , SUFU ( SuFu homolog ) , DZIP 1 ( Iguana homolog ) , GLI 1 , GLI 2 and GLI 3 ( Cubitus interruptus homologs ) are implicated in the Hedgehog signaling . ^^^ SHH up regulation , IHH upregulation and HHIP down regulation lead to aberrant activation of Hedgehog signaling through PTCH 1 to GLI 1 in gastric cancer . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| In contrast , mice lacking one or two functional Ink4c alleles and one copy of Patched ( Ptc 1 ) encoding the Shh receptor rapidly developed MBs that retained wild type p 53 . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Hedgehog interacting protein ( Hip ) and Patched 1 ( Ptc 1 ) regulate the cell responses to the morphogen Sonic Hedgehog ( Shh ) . ^^^ Here , we compare the relative expression patterns of Shh , Hip and Ptc 1 transcripts in the E13 . 5 mouse brain embryo . ^^^ We observe that the expression of Hip and Ptc 1 often overlaps and is found close to Shh expressing cells , suggesting that both proteins are required for controlling Shh signals . ^^^ These data raise the hypothesis for a functional link between nitric oxide and Shh signaling and for a nonredundant role of Hip and Ptc 1 in the adult brain . . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Mutations of the Sonic hedgehog ( SHH ) receptor , Patched 1 ( PTCH 1 ) , have been identified in a variety of tumors . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The expression patterns of the Sonic hedgehog signaling cascade genes ( Shh , Ptc 1 and Gli 1 ) were mostly unchanged in the in situ hybridization , but the quantitative expressions of Ptc 1 and Gli 1 were increased in real time reverse transcriptase polymerase chain reaction analyses , quite contrary to the findings of a previous study using chick embryos . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The morphogen , Sonic hedgehog ( Shh ) , is a crucial regulator of these processes , along with its down stream targets patched ( Ptc ) , Hox , bone morphogenetic proteins ( BMP ' s ) , vascular endothelial growth factor ( VEGF ) and nitric oxide synthase ( NOS ) . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| In mice , disruption of Ink4c collaborates independently with loss of p 53 or with inactivation of the gene ( Ptc 1 ) encoding the Shh receptor , Patched , to induce MB formation . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The initial part of this process is accomplished by Shh acting through Patched ( Ptc ) to regulate Smoothened ( Smo ) activity . ^^^ Recently , a forward genetic approach in mice identified a role for intraflagellar transport ( IFT ) genes in Shh signal transduction , downstream of Patched ( Ptc ) and Rab 23 . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| This is accompanied by a severe depletion of medial cell populations that encounter high concentrations of SHH , an expansion of lateral cell populations that experience low concentrations of SHH and a broad deregulation of HH ' s principal effectors ( PTC 1 , GLI 1 , GLI 2 , GLI 3 ) . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We detect expression of Shh , PTCH 1 and Gli 1 in 115 cases of HCC and in 44 liver tissues adjacent to the tumor . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Stimulation of wild type MEFs by Sonic Hedgehog ( Shh ) peptide elicited unique profiles of induction of Hedgehog target genes Gli 1 , Ptc 1 , and Hip 1 . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| METHODS AND RESULTS : We first found that Shh , its receptors Patched 1 ( Ptc 1 ) as well as Smoothened ( Smo ) and its downstream transcription factor Gli 1 were expressed in the basal layer of human fetal epidermis and freshly sorted HPESCs . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Though mutations of the genes , PTCH 1 and SMO , are known to be involved in aberrant Shh signalling , the distinct downstream effectors of these genes are poorly described . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Abbreviations used : BrdU , 5 bromo 2 ' deoxyuridine ; HERS , Hertwig ' s epithelial root sheath ; NFI C / CTF , nuclear factor Ic / CAAT box transcription factor ; PCNA , proliferating cell nuclear antigen ; Ptc , patched ; Shh , sonic hedgehog ; Smo , smoothened . . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The Shh receptor Patched 1 ( Ptch 1 ) and its downstream effector Smoothened ( Smo ) were initial prime suspects as they are membrane proteins whose cellular dynamics are modulated by the Shh signal . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| We found that the expression of these genes was markedly induced while that of Shh or Ptch 1 , Ptch 2 was not . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| A total of 106 uterine cervical cancers and related lesions ( 37 squamous cell carcinomas , 23 cervical intraepithelial neoplasia ( CIN ) 3 , 10 CIN 2 , four CIN 1 , 32 normal cervical epithelia ) were immunohistochemically analyzed with anti Shh , Indian Hh ( Ihh ) , Patched ( PTCH ) , Smoothened ( Smo ) , Gli 1 , Gli 2 , Gli 3 antibodies on paraffin blocks . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| IHH , SHH , Patched ( PTCH ) , Smoothened ( SMO ) , and downstream targets were expressed more frequently and highly in the diffuse as compared with intestinal type cancers . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The sonic hedgehog ( SHH ) receptor Patched 1 ( Ptch 1 ) is critical for embryonic development , and its loss is linked to tumorigenesis . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| The understanding of mutations that are known to activate hedgehog ( Hh ) signalling pathway genes , including PATCHED ( PTCH ) , sonic hedgehog ( Shh ) and smoothened ( Smo ) , has substantially expanded our current understanding of the genetic basis of BCC development . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| Furthermore , expression of sonic hedgehog protein is detected in majority of PTCH 1 positive tumors ( 24 out of 27 ) . ^^^ |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: Q15465 and Q13635 |
Pubmed |
SVM Score :0.0 |
| NA |
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