| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.80918412 |
| Rap 1 is activated by CRK adaptor proteins and the guanine nucleotide exchange factor C3G , and forms a stable complex with B Raf , an activator of MAP kinase . 0.80918412^^^ |
|
| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.59288327 |
| Furthermore , we found that Rap 1 was overexpressed and formed a complex with B Raf in melanoma cell lines with a V599E mutation of B Raf . 0.59288327^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| Here we have used this assay system and examined the effect of Rap 1 on the B Raf activity to phosphorylate recombinant MAP kinase kinase ( MEK ) . ^^^ These results indicate that not only Ras but also Rap 1 is involved in the activation of the B Raf dependent MAP kinase cascade . . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| AMP activates MAP kinase and Elk 1 through a B Raf and Rap 1 dependent pathway . ^^^ These cell type specific actions of cAMP require the expression of the serine / threonine kinase B Raf and activation of the small G protein Rap 1 . ^^^ Rap 1 , activated by mutation or by the cAMP dependent protein kinase PKA , is a selective activator of B Raf and an inhibitor of Raf 1 . ^^^ Therefore , in B Raf expressing cells , the activation of Rap 1 provides a mechanism for tissue specific regulation of cell growth and differentiation via MAP kinase . . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| On the other hand , B Raf , another Raf family member , is activatable by both Ras and Rap1A . ^^^ When interactions with Ras and Rap1A were measured , B Raf CRD did not exhibit the enhanced interaction with Rap1A , suggesting that the strength of interaction at CRDs may account for the differential action of Rap1A on Raf 1 and B Raf . ^^^ The importance of the interaction at the CRD is further supported by a domain shuffling experiment between Raf 1 and B Raf , which clearly indicated that the nature of CRD determines the specificity of response to Rap1A : Raf 1 , whose CRD is replaced by B Raf CRD , became activatable by Rap1A , whereas B Raf , whose CRD is replaced by Raf 1 CRD , lost its response to Rap1A . ^^^ Finally , a B Raf CRD mutant whose interaction with Rap1A is selectively enhanced was isolated and found to possess the double mutation K252E / M278T . ^^^ B Raf carrying this mutation was not activated by Rap1A but retained its response to Ras . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| However , rap 1 mediates A ( 2A ) receptor dependent activation of MAP kinase only in CHO cells , the signaling cascade being composed of G ( s ) , adenylyl cyclase , rap 1 , and the p 68 isoform of B raf . ^^^ In spite of the close homology between p 21 ( ras ) and rap 1 , the S17N mutant of rap 1 was not dominant negative because ( 1 ) overexpression of rap 1 ( S17N ) failed to inhibit A ( 2A ) receptor dependent MAP kinase activation , ( 2 ) rap 1 ( S17N ) was recovered in the active form with a GST fusion protein comprising the rap 1 binding domain of ralGDS after A ( 2A ) receptor activation , and ( 3 ) A ( 2A ) agonists promoted the association of rap 1 ( S17N ) with the 68 kDa isoform of B raf in CHO cells . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| Neuronal calcium activates a Rap 1 and B Raf signaling pathway via the cyclic adenosine monophosphate dependent protein kinase . ^^^ In the present study , we describe a protein kinase A ( PKA ) dependent signaling pathway that may link neuronal calcium influx to ERKs via the small G protein , Rap 1 , and the neuronal Raf isoform , B Raf . ^^^ Furthermore , depolarization also induced the PKA dependent stimulation of Rap 1 and led to the formation of a Rap1 / B Raf signaling complex . ^^^ Given the fact that both Rap 1 and B Raf are highly expressed in the central nervous system , we suggest that this signaling pathway may regulate a number of activity dependent neuronal functions . . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| ERKs ) via the small G protein rap 1 and the serine / threonine kinase B Raf . ^^^ Interestingly , beta ( 2 ) AR activates both the small G proteins Rap 1 and Ras , but only Rap 1 is capable of coupling to Raf isoforms . beta ( 2 ) AR inhibits the Ras dependent activation of both Raf isoforms Raf 1 and B Raf , whereas Rap 1 activation by isoproterenol recruits and activates B Raf . beta ( 2 ) AR activation of ERKs is not blocked by expression of RasN 17 , an interfering mutant of Ras , but is blocked by expression of either RapN 17 or Rap1GAP1 , both of which interfere with Rap 1 signaling . ^^^ We propose that isoproterenol can activate ERKs via Rap 1 and B Raf in these cells . . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| The intracellular localization of endogenous 14 3 3 theta , B Raf , and Rap 1 was analyzed in distinct spermatogenic cell types and a peculiar codistribution of the three proteins was immunorevealed in differentiating spermatids . ^^^ Together , these data demonstrate that a protein complex formed by endogenous Rap 1 , 93 to 95 kDa B Raf , and 14 3 3 theta exists in vivo and the finding that this has been detected in cytodifferentiating , not dividing cells , strengthens the hypothesis for a role of Rap1 / B Raf mediated signaling in cell morphogenesis and differentiation . . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| Cyclic AMP can either activate or inhibit the mitogen activated protein kinase ( MAPK ) pathway in different cell types ; MAPK activation has been observed in B Raf expressing cells and has been attributed to Rap 1 activation with subsequent B Raf activation , whereas MAPK inhibition has been observed in cells lacking B Raf and has been attributed to cAMP dependent protein kinase ( protein kinase A ) mediated phosphorylation and inhibition of Raf 1 kinase . ^^^ In all four cell types , cAMP activated Rap 1 , and the 95 and 68 kDa isoforms of B Raf were expressed . cAMP activation or inhibition of MAPK correlated with activation or inhibition of endogenous and transfected B Raf kinase . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| Similarly to previously identified Rap GEFs , C3G and Smg GDS , each of the newly identified exchange factors promoted the activation of Elk 1 in the LNCaP prostate tumor cell line where B Raf can couple Rap 1 to the extracellular receptor activated kinase cascade . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| This pathway involves the PKA dependent activation of the Ras related small G protein , Rap 1 , and subsequent stimulation of the neuronal Raf isoform , B Raf . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| Although not necessary for signaling to ERK in primary fibroblasts , FAK may enhance and prolong integrin mediated activation of ERK through p 130 ( CAS ) , Crk , and Rap 1 in cells expressing B Raf . . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| Embryonic fibroblasts from b raf knockout mice showed a bombesin inducible Erk phosphorylation , providing evidence that B Raf does not link Rap 1 to Erk activation in bombesin stimulated fibroblasts . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| RA GEF 1 , a guanine nucleotide exchange factor for Rap 1 , is activated by translocation induced by association with Rap1 * GTP and enhances Rap 1 dependent B Raf activation . ^^^ Correspondingly , when coexpressed with wild type Rap 1 , RA GEF 1DeltaRA is unable to further activate B Raf , whereas RA GEF 1 stimulates B Raf as efficiently as activated Rap 1 . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| The activation of Rap 1 and B Raf was involved in the mechanism of MAP kinase stimulation by TSH . ^^^ After a 3 min exposure to FSK , B Raf was recruited to a vesicular compartment , where it colocalized with Rap 1 . ^^^ Both activation of Rap 1 and translocation of B Raf were PKA independent . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| We found that H . pylori infection of gastric epithelial cells activated the MEK 1 2 / ERK1 2 cascade through cAMP dependent stimulation of Rap 1 and B Raf , but not Ras / c Raf 1 , leading to potent transactivation of the human HDC promoter . ^^^ Thus , our studies demonstrate for the first time to our knowledge that the GalphaS > cAMP > Rap 1 > B Raf > MEK1 / 2 > ERK1 / 2 pathway is critical for H . pylori dependent epithelial gene regulation , which can be induced via a bioactive component ( s ) apart from the site of bacterial colonization . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| The small G protein RAP 1 and the kinase B RAF have been proposed to link elevations of cAMP to activation of ERK / mitogen activated protein ( MAP ) kinase . ^^^ In CHO A ( 2A ) cells , the stimulation of the A ( 2A ) receptor resulted in an activation of RAP 1 and formation of RAP 1 B RAF complexes . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| Finally , we have shown that GIP regulation of the ERK1 / 2 module is via Rap 1 but does not involve Gbetagamma subunits nor Src tyrosine kinase , and we propose that cAMP based regulation occurs via B Raf in both CHO K 1 and beta cells . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| Rheb , like Ras and Rap 1 , bound B Raf kinase , but in contrast to Ras and Rap 1 , Rheb inhibited B Raf kinase activity and prevented B Raf dependent activation of the transcription factor Elk 1 . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| In HEK 293 cells , isoproterenol activates Rap 1 , stimulates Rap 1 association with B Raf , and activates ERKs , all via PKA . ^^^ Furthermore , a Src mutant ( SrcS17D ) , which mimics PKA phosphorylation at serine 17 , stimulates Rap 1 activation , Rap1 / B Raf association , and ERK activation but does not stimulate Ras or AKT . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| In contrast to Raf 1 , B Raf is activated by Rap 1 . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| Although direct connections of Rap 1 with the serine / threonine kinases Raf 1 and B raf have been reported , we were unable to find functional evidence for an interaction of endogenous Rap 1 signalling with the Raf / extracellular signal regulated kinase ( ERK ) pathway . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| METHODS : Kidneys of 8 week old normal Han : SPRD rats ( + / + ) or rats heterozygous ( Cy / + ) for ADPKD were examined by Western blot analysis and immunohistochemistry to determine the expression of extracellular regulated kinase ( ERK ) , phosphorylated ERK ( P ERK ) , Raf 1 ( MAPKKK ) , phosphorylated Raf 1 ( P Raf 1 ) , B Raf , Rap 1 and phosphorylated protein kinase A ( P PKA ) . ^^^ We suggest that cAMP , acting through PKA , Rap 1 and B Raf , may contribute to the activation of ERK in a way that complements receptor tyrosine kinase mediated agonists in the promotion of cyst enlargement . . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| Antibodies against the monomeric G protein Ras or the kinase Raf 1 curtailed the stimulation of H K ATPase by isoproterenol , whereas antibodies against the related proteins Rap 1 and B Raf had no effect . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| Furthermore , VIP induced the activation of the small GTPase Rap 1 and of a 95 kDa isoform of the serine / threonine kinase B Raf . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| Recent studies suggest that Rap 1 can activate the MAP kinase kinase kinase B Raf that is either endogenously or ectopically expressed . ^^^ Peripheral T cells generally do not express B Raf ; therefore , to test the hypothesis that ectopic expression of B Raf could permit Rap 1 to activate ERK signaling , we generated transgenic mice expressing B Raf within peripheral T cells . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| Somatostatin receptor inhibits cell proliferation through Ras , Rap 1 , and B Raf dependent ERK 2 activation . ^^^ In addition , using dominant negative mutants , we show that sst 2 mediated ERK 2 stimulation is dependent on the pertussis toxin sensitive Gi / o protein , the tyrosine kinase Src , both small G proteins Ras and Rap 1 , and the MEK kinase B Raf but is independent of Raf 1 . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| The effectors that mediate Rap 1 signaling have not yet been definitely identified , with the exception of B Raf which , however , is restricted to neuronal tissues and a small subset of other cell types , including in particular male germ cells . ^^^ We previously showed that in mouse spermatids Rap 1 could interact with B Raf giving rise to a signaling complex . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| Western blot analysis revealed that NHK expressed B Raf and Rap 1 . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| BCR / ABL activates Rap 1 and B Raf to stimulate the MEK / Erk signaling pathway in hematopoietic cells . ^^^ BCR / ABL also activated in a kinase activity dependent manner the B Raf kinase , which is an effector molecule of Rap 1 and a potent activator of the MEK / Erk / Elk 1 signaling pathway . ^^^ Together , these data suggest that , in addition to the well established Ras / Raf 1 pathway , BCR / ABL activates the alternative signaling pathway involving Rap 1 and B Raf to activate Erk , which may play important roles in leukemogenesis . . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| In microcystin transformed cells , PI3K , MAPKAPK 2 , Akt , cyclin D 1 and cyclin D 3 in the Akt pathway ; IQGAP 2 , RabGTPase , Rap1GAP , RasGAP , R Ras , Krev 1 and TC 21 of the Ras GTP / GDP protein family ; and A Raf , B Raf and PAK in the Ras / MAPK pathway were all markedly upregulated . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| These actions of Rap 1 occur in selected cell types to enhance or diminish ERK signaling , depending on the expression pattern of the MAP kinase kinase kinases of the Raf family : Raf 1 and B Raf . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| OBJECTIVE / DESIGN / PATIENTS : In an attempt to clarify such controversies and to find whether or not FVPTC cases share the molecular features of follicular tumors , we searched for the presence of PAX 8 PPARgamma rearrangements , RAS mutations , and RAP 1 , RAF 1 , and BRAF mutations in a series of 40 FVPTCs as well as in 27 follicular thyroid carcinomas ( FTCs ) and 12 follicular thyroid adenomas ( FTAs ) . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| Moreover , inactivation or depletion of PKA did not affect Rap 1 activity , and Rap 1 depletion did not affect either B Raf activity or ERK1 / 2 activation . ^^^ This ruled out a role for Rap 1 in the PKA mediated B Raf / ERK activation in ( WT ) B Raf cells . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| Rap 1 activation by Epac CAAX , but not wild type Epac , triggers its association with B Raf . ^^^ This activation requires the GTP dependent association of Rap 1 with B Raf . ^^^ These data demonstrate that B Raf is a physiological target of Rap 1 , but its utilization as a Rap 1 effector is GEF specific . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| BCR / ABL and IL 3 activate Rap 1 to stimulate the B Raf / MEK / Erk and Akt signaling pathways and to regulate proliferation , apoptosis , and adhesion . ^^^ Here , we demonstrate that the abrogation of Rap 1 activation by SPA 1 , a Rap 1 specific GAP , inhibits activation of B Raf , MEK , Erk , and Akt in a murine hematopoietic cell line , Ton . ^^^ Thus , IL 3 or BCR / ABL induced activation of Rap 1 may play important roles in regulation of cell proliferation and survival through activation of the B Raf / MEK / Erk and Akt signaling pathways and in induction of integrin mediated cell adhesion . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| In contrast , components of the PKA independent ( Epac ) pathway , including Rap 1 or B Raf , were not phosphorylated by strain . ^^^ |
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| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P62834 |
Pubmed |
SVM Score :0.0 |
| NA |
|