| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| It is not known whether this GGF like activity is neuregulin 1 ( NRG 1 ) , an epidermal growth factor ( EGF ) related molecule that regulates the proliferation , survival , and differentiation of developing Schwann cells , the related factor NRG 2 , or another NRG / EGF ligand . ^^^ |
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| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND & AIMS : It was recently reported that human gastric lipase ( HGL ) activity is modulated by epidermal growth factor ( EGF ) . ^^^ The aims of this study were to establish the cellular localization of HGL , to assess the correlation between HGL messenger RNA ( mRNA ) and protein levels , and to establish the molecular mechanism of action of EGF and its homologue transforming growth factor alpha ( TGF alpha ) on HGL expression . ^^^ EGF and / or TGF alpha down regulated HGL mRNA levels and decreased enzymic activity . ^^^ The role of the mitogen activated protein kinase cascade in the regulation of HGL expression was highlighted by the use of MAP kinase kinase 1 / 2 inhibitor PD 98059 , which blunted both the activation of p42 / p44 ( mapk ) and the down regulation of HGL mRNA induced by EGF and / or TGF alpha . ^^^ CONCLUSIONS : The expression of HGL is regulated at the mRNA level , and the down regulatory action of EGF and / or TGF alpha on HGL involves the stimulation of p42 / p44 ( mapk ) cascade . . ^^^ |
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| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Neuregulin ( also called NDF , heregulin , GGF and ARIA ) is a member of the EGF family which induces growth and differentiation of epithelial , glial and muscle cells in culture . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| These observations are consistent with the proposal that GGF 1 , GGF 2 , and GGF 3 are a set of potent glial cell mitogens and putative ligands of members of the EGF receptor family , namely p 185 neu / erbB2 , p160 / erbB3 , and p180 / erbB4 , which may play important roles in the development , regeneration , and tumor biology of the peripheral nervous system . . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Their functionality was demonstrated by the presence of zonulae occludens and adherens at cell to cell contacts , [ ( 3 ) H ] thymidine incorporation , Periodic acid Schiff staining , and expression of growth factor receptors ( EGF / TGFalpha , IGF 1 , HGF , KGF ) , gastric H ( + ) / K ( + ) ATPase , pepsinogen ( Pg 5 ) , and human gastric lipase ( HGL ) . ^^^ Chief cells were able to produce and secrete both Pg 5 and HGL and to respond to EGF treatment . ^^^ |
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| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Furthermore , EGF downregulates HGL expression at the mRNA level via the p42 / 44 ( MAPK ) pathway without affecting Pg 5 . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| The addition of epidermal growth factor ( EGF ) to post confluent NCI N 87 cells , which exhibit an abundant membrane staining for EGF receptors , modulated HGL activity without affecting Pg 5 . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| There was no significant association between AR , HRG , and CR 1 expression and nodal status , EGF receptor , or c erbB 2 protooncogene expression in these tumors . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| In addition , we found that NDF / HRG can substitute for either EGF or IGF 1 to stimulate proliferation of these cells . ^^^ The ability to substitute for both EGF and IGF 1 is a unique property of NDF / HRG and is not shared by other members of the EGF or IGF family of growth factors , nor by other factors that we have studied . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Two chimeric heregulin toxin fusions consisting of the EGF like receptor recognition domain of the heregulin isoforms HRG alpha and HRG beta 1 , and the domains 2 , Ib and 3 of the Pseudomonas exotoxin A ( ETA ) were constructed . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| A number of different epidermal growth factor ( EGF ) related peptides such as EGF , transforming growth factor alpha ( TGF alpha ) , amphiregulin ( AR ) , heregulin ( HRG ) , and cripto 1 ( CR 1 ) , are coexpressed to varying degrees in both normal and malignant mammary epithelial cells . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| The biological responses to HRG were also compared to EGF and to the growth inhibitory anti ErbB 2 antibody , 4D5 . ^^^ On each cell line tested , the HRG effects were distinguishable from EGF and 4D5 . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| The activation of PI3K in these cells was also associated with high level mitogenic responsiveness to HRG , as well as the IGF / EGF independent proliferation of the 21MT cell lines in culture . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| The EGF family of proteins encompasses several polypeptides such as epidermal growth factor ( EGF ) , transforming growth factor alpha ( TGF alpha ) , amphiregulin ( AR ) and heregulin ( HRG beta 1 ) . ^^^ In contrast to EGF and AR , HRG had no effect on gelatinase induction . ^^^ While a relatively specific inhibitor of EGF receptor tyrosine kinase , PD 153035 , inhibited EGF , AR and HRG induced cell proliferation , it had no effect on MMP 9 induced by EGF and AR . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| A series of chimeric structural genes was generated by in vitro replacement of hEGF sequence with analogous segments from the EGF like domain of human heregulin ( HRG ) , significantly altering the electrostatic character of the amino terminal region of the mature protein . ^^^ Quantitation of HRG / EGF protein in E . coli periplasmic extracts , by RP HPLC , showed a fourfold decrease after one of two acidic residues located in the amino terminal region of the mature hEGF , near the PhoA junction , was replaced . ^^^ Further extension of the amino terminal HRG sequence , beyond the first six residues , resulted in net neutralization of a more distant EGF acidic residue with no additional effect on protein yield . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Interleukin 3 ( IL 3 ) dependent murine 32D cells do not detectably express epidermal growth factor receptors ( EGFRs ) and do not proliferate in response to EGF , heregulin ( HRG ) or other known EGF like ligands . ^^^ E2 / E3 cells were displaced by HRG and betacellulin ( BTC ) but not by other EGF like ligands that were analyzed . ^^^ EGF , BTC and HRG also induced receptor tyrosine phosphorylation , activation of downstream signaling molecules and proliferation of 32D . ^^^ However , EGF and BTC were as effective as HRG in mediating signaling when ErbB 2 was co expressed with the chimera in the 32D . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Eight chimeric toxins composed of the extracellular and EGF like domains of four different HRG isoforms and truncated Pseudomonas exotoxin ( PE38KDEL ) were constructed . ^^^ The EGF like domain of HRG 13 and HRGbeta 2 fused to PE38KDEL showed the highest cytotoxic activity , with a IC 50 of < or = 0 . 001 ng / ml . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Individual residues of the heregulinbeta ( HRG ) egf domain were mutated to alanine and displayed monovalently on phagemid particles as gene 3 fusion proteins . ^^^ Many residues important for HRG binding to its receptors correspond to critical residues for epidermal growth factor ( EGF ) and transforming growth factor alpha binding to the EGF receptor . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| EGF signals through EGFR , whereas heregulin ( HRG ) signaling is initiated through binding to either ErbB 3 or ErbB 4 . ^^^ The same mutant SHP 2 structures that inhibited EGF mediated stimulation of MAPK also blocked HRG alpha / beta induced MAPK activation . ^^^ EGF or HRG beta caused SHP 2 SH 2 domains to engage multiple phosphotyrosine proteins , and mutation of either domain disrupted these associations . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| The EGF like family of proteins , such as epidermal growth factor ( EGF ) , transforming growth factor alpha ( TGFalpha ) , amphiregulin ( AR ) , betacellulin ( BTC ) , cripto 1 ( CR 1 ) , and heregulin ( HRG ) , plays an important role in the pathogenesis of several human carcinomas as autocrine growth factors . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| ErbB 3 was phosphorylated in vivo in response to either heregulin ( HRG ) in cells expressing both ErbB 3 and ErbB 2 , or epidermal growth factor ( EGF ) in cells expressing both ErbB 3 and EGF receptor . ^^^ A recombinant receptor protein ( ErbB 3 K / M , in which K / M stands for Lys > Met amino acid substitution ) containing an inactivating mutation in the putative ATP binding site was also phosphorylated in response to HRG and EGF . ^^^ Separate kinase inactivating mutations in the EGF receptor and ErbB 2 proteins abolished ErbB 3 phosphorylation and signal transduction activated by EGF and HRG respectively . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Expression of mRNA for heregulin ( HRG ) , a member of the epidermal growth factor ( EGF ) family and its receptors , ErbB 3 and ErbB 4 , were evaluated in human upper gastrointestinal ( GI ) mucosa . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| To study mammary gland expression of the epithelium restricted Ets factor , ESX , mouse cDNA and genomic sequences were cloned and a approximately 350 bp proximal promoter region with > 80 % mouse human homology was identified that mediates ESX induction by serum , heregulin ( HRG ) , or epidermal growth factor ( EGF ) . ^^^ Similarly , cultured HC 11 cells from midpregnant mouse mammary epithelium show an increase in ESX expression upon reaching lactogenic competency ( in the presence of EGF or HRG ) , with a decline to barely detectable levels upon exposure to lactogenic hormones that induce milk protein ( beta casein ) expression . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| We used a weighted evolutionary trace analysis to identify structural features that distinguish the EGF like domain ( hrg ) of heregulins from other members of the EGF family . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| We investigated their mechanism of activation by exogenous EGF and heregulin ( HRG ) in human ovarian carcinoma cell lines which express different amounts and combinations of the four receptors . ^^^ Both EGF and HRG induced activation of mitogen activated protein kinase ( MAPK ) , but the time course of MAPK activation differed depending on the hetero dimers induced . ^^^ EGF and HRG mediated cell growth through the EGFR / HER2 heterodimer and HER 4 , respectively , but not through HER 3 when it was the only HRG receptor expressed and phosphorylated in the cells . ^^^ Moreover EGF and HRG can exert distinct biological functions depending on the receptor complexes induced in a given ovarian cancer cell line . . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| The nontransformed H16N 2 cells isolated from normal tissue express EGFR , p 185 ( erbB 2 ) , and erbB 3 , and are highly responsive to the mitogenic effects of HRG beta as well as to the combination of EGF and insulin in serum free culture . ^^^ HRG beta was also a more potent inducer of p 85 recruited by tyrosine phosphorylated proteins than was either EGF , insulin , or EGF and insulin combined . ^^^ Furthermore , erbB 3 principally mediated the direct recruitment of p 85 in cells stimulated by HRG or EGF , indicating that , in addition to the high level activation of PI3K by p 185 ( erbB 2 ) / erbB 3 , EGFR / erbB 3 heterodimer interaction is essential for the weak but significant level of PI3K activated by EGF in cells that express normal EGFR levels . ^^^ Studies using the PI3K inhibitor wortmannin also indicated that PI3K activation was required for the proliferation of H16N 2 cells induced by either HRG beta or EGF and insulin in serum free culture . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Heregulin beta 1 ( HRG beta 1 ; selective c erbB3 / B4 ligand ) was found to stimulate proliferation in the majority of cell lines , whereas epidermal growth factor ( EGF ; EGFR ligand ) and betacellulin ( BTC ; EGFR / B4 ligand ) induced variable responses . ^^^ HRG beta 1 was less active than EGF and BTC at the optimal concentration ( relative potency of EGF : BTC : HRG = 3 : 4 : 1 ) . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| The HER 3 ECD , purified from Drosophila S 2 cells , binds the EGF like domain of heregulin ( hrg ) with a K ( d ) of 1 . 9 nM as measured by surface plasmon resonance ( SPR ) studies . ^^^ This self association of the HER 3 ECD was reversed by the addition of hrg but not by EGF . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| We demonstrate that mRNAs for the 6 major c erbB ligands , namely , epidermal growth factor ( EGF ) , transforming growth factor alpha ( TGF alpha ) , betacellulin ( BTC ) , heparin binding epidermal growth factor like growth factor ( HB EGF ) , amphiregulin ( AR ) and heregulin ( HRG ) , are expressed in a large panel of HNSCC cell lines . ^^^ HB EGF and HRG mRNAs were induced rapidly ( within 1 hr ) and to a greater extent ( 3 . 2 6 . 2 and 4 . 8 7 . 3 fold increase ) than TGF alpha , BTC and AR mRNAs ( 1 . 6 2 . 7 , 1 . 8 3 . 6 and 1 . 6 4 . 2 fold , respectively ) . ^^^ |
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| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Both EGF and heregulin beta 1 ( HRG ) induced EF 1alpha promoter activity and mRNA and protein expression . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Neither EGF nor heregulin ( HRG ) induced c erbB2 / c erbB 3 receptor complexes in BT 474 . ^^^ However , SK BR 3 cells exhibited a high amount of c erbB2 / c erbB 3 heterodimers even without growth factor stimulation which could be elevated after prolonged EGF and HRG treatment . ^^^ In both cell lines , mitogen activated protein kinase ( MAPK ) phosphorylation was detectable after short term and prolonged EGF and HRG treatment . ^^^ |
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| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| We show that the EGF like domain of heregulin ( hrg ) binds to domains 1 and 2 of HER 3 , in contrast to the EGF receptor , for which prior studies have shown that a construct consisting of domains 3 and portions of domain 4 binds EGF . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Binding of H181T8 , which contains HRG beta 1 residues 177 181 , induced rapid autophosphorylation of EGFR , but in contrast to a previously described chimeric ligand based on EGF was unable to activate other ErbB receptors . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| The PI3K , MAPK and p38MAPK pathways each displayed distinct activation profiles in response to either HRG or EGF , with obvious differences in both the intensity and duration of signal output . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| The development of the mouse mammary gland requires the interaction between several different ovarian and pituitary hormones such as estrogen , progesterone and prolactin as well as several locally derived growth factors in the mammary gland such as epidermal growth factor ( EGF ) , transforming growth factor alpha ( TGFalpha ) , amphiregulin ( AR ) and heregulin ( HRG ) . ^^^ |
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| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| We have investigated the protein expression pattern of the four ErbB receptors EGFR , Her 2 / neu , Her 3 and Her 4 , and correlated it with their putative ligands EGF , TGF alpha and HRG in 74 women with invasive breast cancer . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Overexpression of human EGF receptor HER 2 ( erbB 2 ) leads to amplified heregulin ( HRG ) signaling , promoting more aggressive breast cancer that is nonresponsive to estrogen and the antiestrogenic drug tamoxifen . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Heregulin ( HRG ) , a member of the epidermal growth factor ( EGF ) family of growth factors , is reported to be a potent mitogen for neonatal rat vestibular sensory epithelium , but its effects in adults are unknown . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| We now show that heregulin ( HRG ) , but not EGF , stimulates p95ErbB2 phosphorylation in BT 474 breast cancer cells . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Tumor cell growth in response to growth factors , such as Heregulin ( HRG ) , epidermal growth factor ( EGF ) , or insulin like growth factor 1 ( IGF 1 ) , was also studied . ^^^ HRG stimulation promoted physical and functional erbB2 / erbB3 interactions and tumor cell growth , whereas no response to EGF or IGF 1 was observed . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| We studied epithelial expression of EGF , transforming growth factor a , amphiregulin , heregulin ( HRG ) , betacellulin ( BTC ) , and their receptors , EGFR , HER 2 , and HER 3 , by immunohistochemical analysis in resected bronchial tissue from 20 subjects with ( forced expiratory volume in 1 second [ FEV ( 1 ) ] < 75 % of predicted value ) and 18 without ( FEV ( 1 ) > 85 % predicted value ) COPD . ^^^ Subgroup analysis showed higher EGFR expression in intact epithelium ( 1 . 4 times ; P pound . 04 ) and higher EGF , BTC , and HRG expression in damaged epithelium ( 1 . 4 1 . 8 times ; P < or= . 05 ) of ex smokers with COPD compared with ex smokers without COPD . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| To address this problem , we use quantitative mass spectrometry to analyze dynamic effects of HER 2 overexpression on phosphotyrosine signaling in human mammary epithelial cells stimulated by epidermal growth factor ( EGF ) or heregulin ( HRG ) . ^^^ Data generated from this analysis reveal that EGF stimulation of HER 2 overexpressing cells activates multiple signaling pathways to stimulate migration , whereas HRG stimulation of these cells results in amplification of a specific subset of the migration signaling network . ^^^ Self organizing map analysis of the phosphoproteomic data set permitted elucidation of network modules differentially regulated in HER 2 overexpressing cells in comparison with parental cells for EGF and HRG treatment . ^^^ |
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| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| EGF family member HRGalpha is the only HRG 1 isoform expressed in the mouse mammary gland and our previous experiments suggest that HRG 1 has a unique role in mammary development . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| To determine the sequences involved in receptor binding , we performed homologue scanning mutagenesis on the EGF domain of HRGalpha using sequences of TGFalpha or EGF . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| In this study , we examined the effects of EGF , TGFalpha , amphiregulin and heregulin alpha ( HRGalpha ) on proliferation , wound closure , and the expression of their receptors c erbB 1 c erbB 4 in primary cultures of human urothelial cells in vitro . ^^^ Under conditions representing intact urothelium , all EGF like growth factors except HRGalpha induced proliferation . ^^^ Excessive production ( e . g . in bladder tumors ) or application of EGF , TGFalpha or amphiregulin , but not HRGalpha may lead to either hyperplasia or a faster repair of damaged urothelium in vivo . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| The deduced structure of the precursor of NDF indicated that it is a transmembrane protein whose extracellular portion contains an EGF like domain that probably functions as a receptor recognition site . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| ErbB 2 becomes rapidly phosphorylated and activated following treatment of many cell lines with epidermal growth factor ( EGF ) or Neu differentiation factor ( NDF ) . ^^^ The precise role of ErbB 2 in the transduction of the signals elicited by EGF and NDF is unclear . ^^^ We conclude that in T47D cells , ErbB 2 is a major NDF signal transducer and a potentiator of the EGF signal . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Treatment with NDF and EGF ( epidermal growth factor ) stimulated cell growth , and in A 549 cells the presence of both factors provided an additive increase in cell growth . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Neu differentiation factor ( NDF , or heregulin ) and epidermal growth factor ( EGF ) are structurally related proteins that bind to distinct members of the ErbB family of receptor tyrosine kinases . ^^^ Here we show that NDF inhibits EGF binding in a cell type specific manner . ^^^ The extent of inhibition correlated with both receptor saturation and affinity of different NDF isoforms , and it was abolished upon overexpression of either EGF receptor or ErbB 2 . ^^^ Binding kinetics and equilibrium analyses indicated that NDF reduced the affinity , rather than the number , of EGF receptors , through an acceleration of the rate of ligand dissociation and deceleration of the association rate . ^^^ On the basis of co immunoprecipitation of EGF and NDF receptors , we attribute the inhibitory effect to the formation of receptor heterodimers . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| The present study addressed the biologic effects of various NDF isoforms on normal EGF dependent epithelial cells , Balb / MK keratinocytes , that can undergo either proliferation or differentiation . ^^^ We found that beta isoforms of NDF induced a mitogenic effect , that was significantly smaller than the maximal response to EGF . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| We have analyzed the effects of Neu differentiation factor ( NDF ) / heregulin , a newly described activating ligand for erbB 2 and other members of the epidermal growth factor ( EGF ) receptor family , on cell growth and the expression of milk proteins in HC 11 cells . ^^^ Both NDF and EGF stimulate HC 11 cell proliferation and promote the responsiveness of HC 11 cells to lactogenic hormones . ^^^ Like EGF , NDF inhibits the DIP induced expression of beta casein at the level of transcription . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NDF contains a receptor binding epidermal growth factor ( EGF ) like domain and is a member of the EGF family . ^^^ Since NDF , HER 2 / neu , and HER 3 are present in skin , and other EGF family members can influence wound keratinocytes in vivo , we investigated whether NDF would stimulate epidermal migration and proliferation in a rabbit ear model of excisional wound repair . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| ErbB 2 is a common auxiliary subunit of NDF and EGF receptors : implications for breast cancer . ^^^ We show that in various cells ErbB 2 can form heterodimers with both EGF receptor ( ErbB 1 ) and NDF receptors ( ErbB 3 and ErbB 4 ) , suggesting that it may affect the action of heterologous ligands without the involvement of a direct ErbB 2 ligand . ^^^ We report that ErbB 2 overexpression enhanced binding affinities to both EGF and NDF , through deceleration of ligand dissociation rates . ^^^ Our results imply that ErbB 2 is a pan ErbB subunit of the high affinity heterodimeric receptors for NDF and EGF . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| While several EGF agonists bind and activate ErbB 1 / EGF receptor , neu differentiation factor ( NDF ) functions as a ligand for ErbB 3 and ErbB 4 . ^^^ We show that all the EGF agonists , but not NDF , stimulated tyrosine phosphorylation of ErbB 1 . ^^^ While EGF , transforming growth factor ( TGF ) alpha , and amphiregulin only had a moderate effect , NDF dramatically increased the ErbB 3 phosphotyrosine content . ^^^ Consequently , only NDF , HB EGF , and BTC significantly stimulated association of phosphatidylinositol kinase activity with ErbB 3 . ^^^ Among the EGF agonists , HB EGF induced a low level of ErbB 4 tyrosine phosphorylation , while BTC was as efficient as NDF in activating ErbB 4 . ^^^ |
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| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| The group of subtype 1 transmembrane tyrosine kinases includes the epidermal growth factor ( EGF ) receptor ( ErbB 1 ) , an orphan receptor ( ErbB 2 ) , and two receptors for the Neu differentiation factor ( NDF / heregulin ) , namely : ErbB 3 and ErbB 4 . ^^^ By using the generated mAbs , we found that the major NDF receptor on mammary epithelial cells is a heterodimer of ErbB 3 with ErbB 2 , whereas an ErbB 1 / ErbB 2 heterodimer , or an ErbB 1 homodimer , is the predominant species that binds EGF . ^^^ Consistent with ErbB 2 being a shared receptor subunit , its tyrosine phosphorylation was increased by both heterologous ligands and it mediated a trans inhibitory effect of NDF on EGF binding . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Interestingly , transphosphorylation between HER 1 and HER 4 can be stimulated by either EGF or NDF . . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| The ErbB family of transmembrane tyrosine kinases includes the receptor for EGF ( ErbB 1 ) , two receptors for NDF / heregulin ( ErbB 3 and ErbB 4 ) and an orphan receptor ( ErbB 2 ) . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Down regulation of cell surface ErbB 1 or ErbB 2 by intracellular expression of specific antibodies has allowed us to delineate the role of these receptors during signaling elicited by : EGF and heparin binding EGF ( HB EGF ) , ligands of ErbB 1 ; betacellulin ( BTC ) , a ligand of ErbB 1 and ErbB 4 ; and neu differentiation factor ( NDF ) , a ligand of ErbB 3 and ErbB 4 . ^^^ Finally , ErbB 1 activated by all EGF related peptides ( EGF , HB EGF , BTC and NDF ) couples to SHC , whereas only ErbB 1 activated by its own ligands associates with and phosphorylates Cbl . ^^^ |
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| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| ErbB 2 is an orphan receptor that belongs to a family of tyrosine kinase receptors for either epidermal growth factor ( EGF ) or Neu differentiation factor ( NDF / neuregulin ) . ^^^ One group of tumor inhibitory mAbs ( Class 2 mAbs ) was elicited by the most antigenic site of ErbB 2 , and inhibited in trans binding of NDF and EGF to their direct receptors . ^^^ The inhibitory effect was due to acceleration of ligand dissociation , and it resulted in the reduction of the ability of ErbB 2 to transactivate the mitogenic signals of NDF and EGF . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Neu differentiation factor ( NDF ) , a member of the epidermal growth factor ( EGF ) related peptide family , activates ErbB 2 via heterodimerization with the NDF receptors ErbB 3 and ErbB 4 . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Neu differentiation factor ( NDF ) is a member of the epidermal growth factor ( EGF ) family of growth factors and is represented by multiple conserved isoforms . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| ODC overexpressing MCF 10A cells exhibited increased MAPK phosphorylation in response to administration of NDF and / or epidermal growth factor ( EGF ) . ^^^ Of note , in the absence of EGF and NDF , ODC overexpression failed to induce both clonogenicity and MAPK activation . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Concentrating on ErbB 1 and two of its ligands , epidermal growth factor ( EGF ) and transforming growth factor alpha ( TGF alpha ) , and the Neu differentiation factor ( NDF / neuregulin ) and one of its receptors , ErbB 3 , we show that ligand binding variably accelerates endocytosis of the respective ligand receptor complex . ^^^ However , unlike the EGF activated ErbB 1 , which is destined primarily to degradation in lysosomes , NDF and TGF alpha direct their receptors to recycling , probably because these ligands dissociate from their receptors earlier along the endocytic pathway . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| This model system allowed the comparison of EGF activated ErbB 1 with ErbB 1 activated by Neu differentiation factor ( NDF ) induced heterodimerization with ErbB 4 . ^^^ Compared to the rapid internalization of EGF activated ErbB 1 , NDF activated ErbB 1 showed delayed internalization characteristics . ^^^ |
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| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Further characterization of the regulation of NDF expression in Balb / MK keratinocytes revealed potent induction by keratinocyte growth factor ( KGF ) and epidermal growth factor ( EGF ) , but not by HGF / NK2 , an alternative HGF isoform with motogenic but not mitogenic or morphogenic activities . ^^^ |
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| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| A2 tumor cells with HER 2 receptor agonists ( EGF and NDF ) enhanced tumor ability to activate CTL from tumor associated lymphocytes ( TAL ) and from T cells from peripheral blood in vitro . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Thus , NTAK is a new member of the EGF family displaying NRG 1 properties . . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| In contrast to previously characterized chimeras of EGF with NRG 1 or TGF alpha , these variants did not only show high binding affinity for ErbB 2 / ErbB 3 heterodimers but also for ErbB 3 alone . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| There are many NRG 1 isoforms , raising the question `` Why so many neuregulins ? ' ' Study of mice with targeted mutations ( `` knockout mice ' ' ) has demonstrated that isoforms differing in their N terminal region or in their epidermal growth factor ( EGF ) like domain differ in their in vivo functions . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| This activation was also encountered in vaginae from neonatally DES exposed mice , along with the expression of EGF , TGF alpha , HB EGF , BTC , APR , EPR and NRG 1 . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| RESULTS : The level of mRNA of 4 ligand genes ( EGF , NRG 1 , NRG 2 and NRG 3 ) was extremely low , that is detectable but not quantifiable . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| AREG ( Amphiregulin ) , BTC ( beta cellulin ) , EGF , EPGN ( Epigen ) , EREG ( Epiregulin ) , HBEGF , NRG 1 , NRG 2 , NRG 3 , NRG 4 and TGFA ( TGFalpha ) constitute EGF family ligands for ERBB family receptors . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| In situ hybridization signals with the unique SMDF sequence probe and with a probe to the conserved EGF like domain are comparable , suggesting that SMDF is the predominant isoform expressed in sensory and motor neurons . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| RESULTS : Expression of all four ErbB receptors and the EGF like ligands EGF , TGF alpha , AR , beta C , Hb EGF , NRG 1 , and NRG 3 was detected in the mouse prostate . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| Wheel running activity was also inhibited by another epidermal growth factor like ( EGF like ) peptide , neuregulin ( NRG 1 ) , that binds to different ErbB receptors . ^^^ |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q02297 and P01133 |
Pubmed |
SVM Score :0.0 |
| NA |
|