| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :1.5875767 |
| B Raf was shown to share almost the same H Ras binding specificity with Raf 1 by examining binding of the H Ras mutants to Raf 1 and B Raf in the yeast two hybrid and in vitro binding assays . 1.5875767^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.92038098 |
| Unexpectedly , yeast two hybrid binding analyses showed that although both Ras and TC 21 could interact with the isolated Ras binding domain of Raf 1 , only Ras interacted with full length Raf 1 , A Raf , or B Raf . 0.92038098^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.67874496 |
| Our results demonstrate an essential role of specific EGF induced Raf 1 phosphorylation sites in Raf 1 activation , identify Raf 1 S 471 as a novel phosphorylation site critical for Raf 1 and B Raf kinase activities , and point to the possibility that the V599E mutation activates B Raf by mimicking a phosphorylation at the S 578 site . . 0.67874496^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.57943252 |
| Mutations of C RAF are rare in human cancer because C RAF has a low basal kinase activity compared with B RAF . 0.57943252^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Human c raf 1 maps to chromosome 3p25 and A raf 1 to Xp 21 . c raf 1 RNA is present in many tissues , while A raf and B raf expression is restricted . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| The gene was termed B raf because it is related to but distinct from c raf and A raf . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| The prototype mitogen activated protein ( MAP ) kinase module is a three kinase cascade consisting of the MAP kinase , extracellular signal regulated protein kinase ( ERK ) 1 or ERK 2 , the MAP / ERK kinase ( MEK ) MEK 1 or MEK 2 , and the MEK kinase , Raf 1 or B Raf . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Differential regulation of Raf 1 and B Raf and Ras dependent activation of mitogen activated protein kinase by cyclic AMP in PC 12 cells . ^^^ Since one of the major differences between the Ras / Raf / MAP kinase cascades of these cell types is the expression of B Raf in PC 12 cells , we compared the effects of cAMP on Raf 1 and B Raf . ^^^ In PC 12 cells maintained in serum containing medium , B Raf was refractory to inhibition by cAMP , whereas Raf 1 was effectively inhibited . ^^^ In contrast , both B Raf and Raf 1 were inhibited by cAMP in serum starved PC 12 cells . ^^^ As in PC 12 cells , B Raf was resistant to inhibition by cAMP in the presence of serum , whereas Raf 1 was effectively inhibited . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Ras proteins function through the formation of specific complexes with Raf 1 , B raf , PI 3 kinase and RalGDS . ^^^ The point mutation at 64 , in combination with additional point mutations at either position 65 or 71 , resulted in a protein which failed to interact with either PI 3 kinase or neurofibromin , though these Ras mutants effectively bound both Raf 1 and B raf . ^^^ Competitive studies with the catalytic domain if neurofibromin , NF 1 GRD , demonstrated that its interaction with Ras GMPPNP is mutually exclusive with both Raf 1 and B raf . ^^^ These data suggest that rasGAP and neurofibromin are unable to downregulate Ras GTP complexed to Raf 1 or B raf . . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Activation of delta Raf 1 : ER and a conditional oncogenic form of B Raf , delta B RAF : ER , resulted in rapid and sustained induction of HB EGF mRNA expression and secretion of mature HB EGF from cells . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| In response to epidermal growth factor , nerve growth factor , and platelet derived growth factor , B Raf and Raf 1 are activated , phosphorylate recombinant kinase inactive MEK 1 , and activate wild type MEK 1 . ^^^ B Raf and Raf 1 are growth factor regulated Raf family members which regulate MEK 1 and MAP kinase activity in PC 12 cells . ^^^ Protein kinase A activation in response to elevated cyclic AMP ( cAMP ) levels inhibited B Raf and Raf 1 stimulation in response to growth factors . ^^^ The results demonstrate that tyrosine kinase receptor activation of MEK 1 and MAP kinase in PC 12 cells is regulated by B Raf and Raf 1 , whose activation is inhibited by protein kinase A , and MEK activators , whose activation is independent of cAMP regulation . . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| In contrast to Raf 1 immunodepleted lysates , preclearance of the cytosolic B Raf significantly reduced , by 96 % , the amount of MEK 1 activity associated with immobilized p21ras . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| C5a receptor ligation activates both B Raf and Raf 1 , with B Raf activation overlapping but temporally distinct from that of Raf 1 . ^^^ B Raf and Raf 1 both efficiently phosphorylate MAP kinase kinase ( MEK 1 ) . ^^^ Activation of both Raf 1 and B Raf was inhibited by protein kinase A stimulation , consistent with the inhibitory effects of increased cAMP levels on neutrophil function . ^^^ The findings define a functional signal transduction pathway linking the neutrophil C5a chemoattractant receptor to the regulation of Ras , B Raf , Raf 1 , and MAP kinase . . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| The raf genes encode for a family of cytoplasmic proteins ( A raf , B raf and c raf 1 ) with associated serine / threonine kinase activities . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| The localizations of two isoenzymes , raf 1 kinase and B raf kinase , were studied with the help of isoenzyme specific polyclonal antibodies . ^^^ The findings indicated that B raf protein kinase and raf 1 kinase are present almost ubiquitously in the neurons of the investigated cortical structures . ^^^ The intensity of staining obtained with serial dilutions of the antibodies indicated that the cytoplasmic concentration of B raf kinase is tended to be higher than that of raf 1 kinase . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| IL 8 stimulation of its receptor on neutrophils activates Ras GTP loading and the mitogen activated protein kinase ( MAPK ) pathway including Raf 1 and B Raf . ^^^ Even though Ras GTP loading is similar for IL 8 and C5a , the maximal activation of Raf 1 and B Raf is approximately 2 fold and 3 7 fold , respectively , less for IL 8 than that observed for C5a . ^^^ IL 8 activation of MAPK follows a time course suggesting an involvement of both Raf 1 and B Raf . ^^^ Surprisingly , wortmannin , at low concentrations , inhibits Raf 1 , B Raf , and MAPK activation in response to IL 8 and C5a demonstrating a role for phosphatidylinositol 3 kinase in the activation of Raf kinases in G protein coupled receptor systems in human neutrophils . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| By using methods based on inhibition of yeast adenylyl cyclase or RasGAP activity and by in vitro binding assays , we have shown that the segment of B Raf corresponding to amino acid 1 326 binds directly to H Ras with a dissociation constant ( Kd ) comparable to that of Raf 1 and that the binding is not significantly affected by the post translational modifications . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Although c Raf and B Raf have been implicated in growth factor induced MEK activation , little is known about A Raf . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| By contrast , B Raf has aspartic acid residues at positions homologous to those of the phosphorylated tyrosines ( at 340 and 341 ) of Raf 1 and displays a high basal level of activity . ^^^ We conclude that tyrosine phosphorylation is an essential component of the mechanism by which Ras activates Raf 1 kinase activity and that steady state activated Ras is insufficient to activate B Raf in vivo . . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Receptor induced activation of other Ser / Thr kinases , such as c Raf , B Raf , Mek 1 , Mek 2 , Mekk , was not affected by wortmannin . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| PC 12 cells express two Raf isoforms , c Raf and B Raf . ^^^ NGF treatment of PC 12 cells resulted in the enhanced phosphorylation of B Raf and c Raf , and both exhibit reduced electrophoretic mobilities following stimulation of the cells . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| In the mouse , the Raf protein kinase family is comprised of three homologous genes , Raf 1 , A Raf and B Raf [ 5 ] which are ubiquitously expressed in the developing embryo [ 7 ] . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Differential regulation of Raf 1 , A Raf , and B Raf by oncogenic ras and tyrosine kinases . ^^^ We have examined whether the other two members of the Raf family , A Raf and B Raf , are regulated in a similar way to Raf 1 . ^^^ These results show that maximal activation of B Raf merely requires signals that generate Ras GTP , whereas activation of Raf 1 and A Raf requires Ras GTP together with signals that lead to their tyrosine phosphorylation . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Interaction of activated Ras with Raf 1 alone may be sufficient for transformation of rat 2 cells . 5 H ras effector mutants have been assessed for transforming activity and for the ability of the encoded proteins to interact with Raf 1 , B Raf , byr 2 , ralGDS , and CDC 25 encoded proteins in the yeast two hybrid system . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| The serine / threonine kinase Raf 1 , as well as the closely related protein B Raf , elicit the ERK cascade of MAP kinases . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| The kinase domain of B Raf is more active than the equivalent portion of Raf 1 which in turn is more active than A Raf . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Moreover , the overexpression of MEK 1 ( 3A ) failed to block endogenous MEK 1 activation , although MEK 1 ( 3A ) formed complexes with both c Raf and B Raf as well as p42 / p44 MAPK . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Treatment of S 49 cells with somatostatin transiently inactivated the basal activity of Raf 1 , but not that of B Raf . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| RESULTS : In the yeast two hybrid interaction assay , mKsr 1 did not bind to either Ras , B Raf or Raf 1 , but interacted strongly with both MEK 1 and MEK 2 , activators of MAP kinase . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NGF treatment of primary cultures of rat hepatocytes with a maximally effective concentration of NGF ( 20 ng / ml , 0 . 8 nM ) caused acute phasic activation of Raf 1 and p 42 ( MAPkinase ) , and a smaller sustained activation of B Raf . ^^^ In contrast to hepatocytes , NGF treatment of PC 12 pheochromocytoma cells caused large sustained activations of B Raf and p 42 ( MAPkinase ) , and a lower phasic activation of Raf 1 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Raf 1 , A Raf and B Raf comprise a small family of highly conserved serine / threonine protein kinases , whose activities play a fundamental role in the control of proliferation and differentiation . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Three isoforms of the Raf family of oncoprotein kinases ( A Raf , B Raf , and Raf 1 or c Raf ) were detected in bovine luteal cells . ^^^ Raf 1 and B Raf , but not A Raf , were activated by PGF2alpha ( 1 microM ) and the pharmacological PKC activator phorbol myristate acetate ( PMA , 20 nM ) . ^^^ In vitro protein kinase assays demonstrated that activation of Raf 1 and B Raf resulted in the phosphorylation and activation of MAPK kinase ( MEK 1 ) , which subsequently phosphorylated p42mapk . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Several recent studies have revealed interesting differences between two members of this family , Raf 1 and B Raf , regarding their activation , regulation , and kinase activity . ^^^ In particular , B Raf was shown to display higher MEK kinase activity than Raf 1 . ^^^ By using both two hybrid analysis and coimmunoprecipitation experiments , we demonstrate here that B Raf also markedly differs from Raf 1 by a higher affinity for MEK . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Similarly , B Raf kinase was not inhibited by G kinase ; the Ser 43 phosphorylation site of c Raf is not conserved in B Raf . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Raf is a member of a multigene family which includes : Raf 1 , A Raf and B Raf . ^^^ Cytokine dependent TF 1 cells were infected with retroviruses encoding amino terminal deleted ( delta ) A Raf , B Raf and Raf 1 proteins . ^^^ This result was unexpected as A Raf is an intrinsically weaker kinase than either Raf 1 or B Raf . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| While activation of the serine / threonine kinases Raf 1 and B Raf has been implicated in signalling pathways leading to transformation by H Ras , it has been argued that TC 21 does not activate Raf 1 or B Raf . ^^^ Raf 1 and B Raf are constitutively active in TC 21 transformed cells and the ERK / MAPK cascade is required for the maintenance of the transformed state . ^^^ We demonstrate that oncogenic V 23 TC21 , like Ras , interacts with Raf 1 and B Raf ( but not with A Raf ) , resulting in the translocation of the Raf proteins to the plasma membrane and in their activation . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Because c Raf activation and MEK activation were inversely affected by PI 3 K and cAMP dependent pathways , we examined whether IL 3 activated the alternative Raf isoforms A Raf and B Raf . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Serine and tyrosine phosphorylations cooperate in Raf 1 , but not B Raf activation . ^^^ While B Raf lacks a tyrosine phosphorylation site equivalent to Y 341 of Raf 1 , S 445 of B Raf is equivalent to S 338 of Raf 1 . ^^^ Thus , there are considerable differences between the activation of the Raf proteins ; Ras GTP mediates two phosphorylation events required for Raf 1 activation but does not regulate such events for B Raf . . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| In contrast to the inhibitory effect of PKA on Raf 1 dependent processes , PKA potentiates nerve growth factor stimulated PC 12 cell differentiation , a B Raf mediated process . ^^^ The kinase domains of Raf 1 and B Raf are highly conserved , and it has been predicted that B Raf catalytic activity would also be inhibited by PKA . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Fractions containing kinase activity were also probed with antibodies against MEK kinase 1 , Raf 1 , A Raf , B Raf , Mos , and Tpl 2 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Raf 1 and B Raf proteins have similar regional distributions but differential subcellular localization in adult rat brain . ^^^ We show that B Raf and Raf 1 proteins are present in most brain areas , whereas A Raf is not detected . ^^^ Raf 1 is localized mainly in the cytosolic fraction around the nucleus , whereas B Raf is widely distributed in the cell bodies and in the neuritic processes . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Activation of MEK is not only necessary but also sufficient for cell survival because overexpression of constitutively activated MEK , Ras , or Raf 1 , like B Raf , prevents apoptosis after growth factor deprivation . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Western immunoblotting confirmed that Raf 1 , A Raf , B Raf , MEKK 1 and MEKK 2 were present at similar levels in E 19 and adult liver . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Thus , in PC 12 cells , depolarization mediated calcium influx led to the activation of B Raf , but not Raf 1 , via PKA . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| The activation of B Raf and Raf 1 after electroconvulsive shock in the rat hippocampus . ^^^ We demonstrated that ECS activates the kinase activity of B Raf and Raf 1 in the rat hippocampus . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| In Chinese hamster ovary cells , EGF receptors activate B Raf but not Raf 1 or A Raf . ^^^ Moreover , Galpha ( o ) Q205L failed to affect MAPK activation by fibroblast growth factor receptors , which stimulate Raf 1 and A Raf but not B Raf activity . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| 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 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| RAF kinase is a family of isoforms including A RAF , B RAF , and C RAF . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| A dominant negative mutant of B Raf , but not of Raf 1 , blocked the cAMP induced activation of ERK , indicating that B Raf is the MEK 1 upstream regulator mediating this cAMP effect . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| There are three Raf family members : A Raf , B Raf and Raf 1 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| One site , Ser ( 364 ) , is conserved with c Raf but two additional sites , Ser ( 428 ) and Thr ( 439 ) , are unique to B Raf . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Deletion analysis , as well as in vitro binding experiments , revealed that RGS 14 binds Rap proteins through a domain distinct from that carrying the RGS identity , and that this domain shares sequence identity with the Ras / Rap binding domain of B Raf and Raf 1 kinases . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
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 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Active Ras induces heterodimerization of cRaf and BRaf . ^^^ Within the mechanism of Raf activation , two isoforms of Raf , cRaf and BRaf , may cooperate . ^^^ We investigated the relationship between cRaf and BRaf and found that active Ras induced heterodimerization of cRaf and BRaf , an effect that was dependent on the serine residue at position 621 of cRAF : Moreover , we also found that cRaf COOH terminus constitutively associated with BRaf , whereas the NH ( 2 ) terminus did not , even in the presence of active RAS : These data suggest that Ras induces the cRaf BRaf complex formation through the exposure of 14 3 3 binding sites in the COOH terminus of cRAF : Thus , Ras induced cRaf Braf heterodimerization may explain the observed cooperativity of cRaf and BRaf in cells responding to growth factor signals . . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Raf and MEK could abrogate the cytokine dependence of murine FDC PI and human TF 1 cells ; however , the frequency of transformation was dependent on the particular oncogene examined , as more factor independent cells were isolated after infection with activated retroviruses encoding A Raf or Raf 1 than were with MEK 1 or B Raf . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Involvement of B Raf in Ras induced Raf 1 activation . ^^^ Immunodepletion of B Raf abolished the effect of the activator on Raf 1 . ^^^ Furthermore , B Raf and Ras activated Raf 1 co operatively , when co transfected into human embryonic kidney 293 cells . ^^^ On the other hand , Ras dependent extracellular signal regulated kinase / mitogen activated protein kinase kinase stimulator ( a complex of B Raf and 14 3 3 ) failed to activate Raf 1 in our cell free system . ^^^ These results suggest that B Raf is an essential component of the Ras dependent Raf 1 activator . . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Interestingly , B Raf and Raf 1 activity towards MEK as measured by the immunoprecipitation kinase cascade assay are both significantly increased in the A Raf deficient MEFs . . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Down stream of PKA , the activity of B Raf was significantly decreased by nicotine in SH SY5Y cells , as determined by direct measurement of MEK 1 phosphorylation or in vitro kinase assays , whereas the modulation of MEK 1 phosphorylation by Raf 1 tended to increase . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Raf comprises a family of three kinases , A Raf , B Raf and Raf 1 , which are best known as key regulators of the MEK MAPK / ERK cascade . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| The binding between A Raf and TH 1 was specific , as no binding between TH 1 and B Raf or c Raf was observed , and the amino terminal 162 amino acids in the A Raf regulatory domain were found to be sufficient for this interaction . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Stimulation of alpha 2 adrenergic receptor inhibits cholangiocarcinoma growth through modulation of Raf 1 and B Raf activities . ^^^ Among Raf proteins , Raf 1 and B Raf differentially regulate mitosis . ^^^ Mz ChA 1 cells expressed Raf 1 and B Raf . ^^^ Epidermal growth factor ( EGF ) immediately and transiently stimulated Raf 1 activity , whereas B Raf activity was increased with prolonged EGF stimulation . ^^^ EGF stimulated Raf 1 and B Raf activities were both inhibited by UK 14 , 304 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Genetic and biochemical approaches have identified Raf family serine / threonine kinases B Raf and C Raf as major mediators of cell survival . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Indeed , this pattern of MAPK activation could be explained by the fact that R Ras 3 was unable to activate c Raf , while it bound and stimulated the neuronal Raf isoform , B Raf , in PC 12 cells . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| B Raf and Raf 1 expression was investigated to assess whether Rap1b effects are mediated via the Raf pathway . ^^^ B Raf , and not Raf 1 , expression was increased in MCs transfected with Rap1b . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| TRH induced c Raf but not B Raf activation , and the D2S receptor inhibited both TRH induced c Raf and basal B Raf kinase activity . ^^^ These results indicate that the dopamine D2S receptor couples to distinct G ( i / o ) proteins , depending on the pathway addressed , and suggest a novel Galpha ( 1 ) 3 / Galpha ( o ) dependent inhibition of MAPK mediated by c Raf and B Raf dependent inhibition of MAPK / ERK kinase . . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| GLP 1 stimulated activation of Erk is blocked by inhibitors of MEK , but GLP 1 does not induce the activation of A Raf , B Raf , C Raf , or Ras . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Inducible gene deletion reveals different roles for B Raf and Raf 1 in B cell antigen receptor signalling . ^^^ B lymphocytes express two Raf isoforms , Raf 1 and B Raf . ^^^ Using an inducible deletion system in DT 40 cells , the contribution of Raf 1 and B Raf to BCR signalling was dissected . ^^^ Loss of Raf 1 has no effect on BCR mediated ERK activation , whereas B Raf deficient DT 40 cells display a reduced basal ERK activity as well as a shortened BCR mediated ERK activation . ^^^ The Raf 1 / B Raf double deficient DT 40 cells show an almost complete block both in ERK activation and in the induction of the immediate early gene products c Fos and Egr 1 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| To investigate the importance of Raf / MEK / ERK signaling in human hematopoietic cell growth , the effects of three different Raf genes , A Raf , B Raf and Raf 1 , on cell cycle progression and regulatory gene expression were examined in TF 1 cells transformed to grow in response to beta estradiol regulated DeltaRaf : ER genes . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Raf 1 , A Raf and B Raf kinase activities were examined in cell lines treated with beta estradiol for 24 hours . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Platelet ERK 2 activation by thrombin is dependent on calcium and conventional protein kinases C but not Raf 1 or B Raf . ^^^ Surprisingly , in contrast to proliferative cells , we found that the serine / threonine kinases Raf 1 and B Raf were not an intermediate kinase between conventional PKCs and MEK1 / 2 . ^^^ After immunoprecipitation of Raf 1 and B Raf , the basal glutathione S transferase MEK 1 phosphorylation observed in resting platelets was not upregulated by thrombin and was still observed in the absence of anti Raf 1 or anti B Raf antibodies . ^^^ Thus in platelets , thrombin induced ERK 2 activation is activated by conventional PKCs independently of Raf 1 and B Raf activation . . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| ERK1 / 2 activation was reduced in the presence of `` dominant negative ' ' Raf 1 ( RafS621A ) and slightly reduced by dominant negative B Raf , indicating the involvement of one or more Raf isoforms . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| In contrast to Raf 1 , B Raf is activated by Rap 1 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
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 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
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 ) . ^^^ B Raf and Raf 1 abundances were greater in Cy / + than in + / + ( 1 . 74 + / 0 . 25 and 1 . 27 + / 0 . 08 fold , respectively ) . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Raf 1 and B Raf , but not A Raf , were activated by EGF ( 10 ng / ml ) and the pharmacological protein kinase C ( PKC ) activator phorbol myristate acetate ( PMA , 20 nM ) . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
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 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| In this study , the effects of activated Raf ( Raf 1 , A Raf and B Raf ) and PI3K / Akt proteins on abrogation of cytokine dependence in FL5 . 12 hematopoietic cells were examined . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| We determined the effects of cAMP and epidermal growth factor ( EGF ) on the activation of ERK , B Raf and Raf 1 in ADPKD and HKC cells by immune kinase assay and Western blot . ^^^ RESULTS : 8 Br cAMP increased phosphorylated ERK ( 2 . 7 + / 0 . 6 fold , N = 7 ) , and B Raf kinase activity ( 3 . 6 + / 1 . 1 fold , N = 5 ) in cells from ADPKD kidneys ; levels of phosphorylated Raf 1 were not changed . ^^^ EGF stimulated the phosphorylation of ERK and Raf 1 in both ADPKD and HKC cells , but had no effect on B Raf . 8 Br cAMP and EGF conjointly increased ERK activation above that of either agonist alone in ADPKD cells , and this combined effect was abolished by PD 98059 , indicating that ERK was activated by EGF and cAMP responsive cascades that converge at MAPK . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Recent studies in mice with targeted mutations of the raf genes have confirmed that B Raf is a far stronger activator of ERKs than its better studied Raf 1 homologue , even in cell types in which the protein is barely expressed . ^^^ The explanation for this lies in a number of key differences in the regulation of B Raf and Raf 1 activity . ^^^ Constitutive phosphorylation of serine 445 of B Raf leads to this protein having a higher basal kinase activity than Raf 1 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| 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 P04049 |
Pubmed |
SVM Score :0.0 |
| Expression and kinase activity of B Raf and Raf 1 in leukemia cell lines ] . ^^^ OBJECTIVE : To study expression and kinase activity of B Raf and Raf 1 kinases in several leukemia cells and normal peripheral blood lymphocytes . ^^^ METHODS : Western blot was carried out to detect expression of B Raf and Raf 1 in peripheral blood lymphocytes and leukemia cells . ^^^ Kinase activities of Raf 1 and B Raf were analyzed by immunoprecipitation and Western blot . ^^^ |
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| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Ser 508 lies within the Raf 1 activation loop , and mutation of this residue in Raf 1 and the equivalent Ser 615 in B Raf revealed that this residue regulates Raf binding to MEK . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Moreover , these results are specific for BRAF , as targeted interference of CRAF in melanoma cells does not significantly alter their biological properties . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Constitutively high ERK , B Raf , and Raf 1 activities were observed in QT RRE cells . ^^^ However , restoration of tuberin expression in QT RRE cells by transient transfection with Tsc 2 cDNA substantially decreased both ERK and B Raf activity , with only modest changes in Raf 1 activity , suggesting tuberin functions as an upstream negative regulator of the ERK pathway . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| FDC P 1 hematopoietic cells were conditionally transformed to grow in response to ( delta ) B Raf : ER , ( delta ) Raf 1 : ER or DA Raf : ER in which the hormone binding domain of the estrogen receptor ( ER ) was linked to the N terminal truncated ( delta ) Raf genes . ^^^ FD / ( delta ) Raf 1 : ER and FD / ( delta ) A Raf : ER , but not FD / ( delta ) B Raf : ER cells , were readily induced to re enter the cell cycle after addition of beta estradiol or IL 3 . ^^^ Deprived FD / ( delta ) Raf 1 : ER , but not FD / ( delta ) B Raf : ER cells , expressed activated forms of MEK 1 and ERK after beta estradiol or IL 3 stimulation . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Recent results have shown that the Raf family isoforms A Raf , B Raf and Raf 1 have different physiological functions . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| B RAF depletion by siRNA blocks ERK activity , whereas A RAF and C RAF depletion do not affect ERK signalling . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| The proliferation of tumour cells containing activating B raf or raf 1 mutations was unaffected by silencing mlk 3 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| We found that SPRY 2 , an inhibitor homologous to SPRY 4 , which was previously shown to suppress Ras / ERK signaling via direct binding to Raf 1 , had reduced expression in WT BRAF cells . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| We found that TCR cross linking could induce up regulation of both B Raf and Raf 1 activities , but Raf 1 activity was decreased rapidly . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| In contrast , immunodepletion of Raf 1 and B Raf , two other MEK activating kinases present in Xenopus egg extracts , had little effect on cyclin stimulated p 42 MAPK activation . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| METHODS : 372 sera of 148 stage 4 melanoma patients and 119 sera of non melanoma patients were screened for B Raf , B Raf V599E and C Raf specific antibodies by an ELISA assay . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| BAY 43 9006 is an oral inhibitor of CRAF , wild type BRAF , mutant V599E BRAF , vascular endothelial growth factor receptor ( VEGFR ) 2 , VEGFR 3 , mVEGFR 2 , FLT 3 , platelet derived growth factor receptor , p 38 , and c kit among other kinases . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| The proliferation of tumor cells with activating mutations in B raf or raf 1 are unaffected by silencing mlk 3 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| In addition , a homology model of Raf 1 was also constructed using the crystal structure of the kinase domain of B Raf isoform with one of the most active Raf 1 inhibitors ( 48 ) inside the active site . ^^^ The ATP binding pocket of Raf 1 is virtually similar to that of B Raf . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| This cell type specificity is explained by the finding that Rit was unable to activate C Raf , while it bound and stimulated the neuronal Raf isoform , B Raf . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Elastin peptides activate extracellular signal regulated kinase 1 / 2 via a Ras independent mechanism requiring both p110gamma / Raf 1 and protein kinase A / B Raf signaling in human skin fibroblasts . ^^^ Together , our results identify a novel Ras independent ERK1 / 2 activation system in which p110gamma / Raf 1 / MEK1 / 2 and PKA / B Raf / MEK1 / 2 cooperate to activate ERK1 / 2 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : Serine threonine kinases of the Raf family ( A Raf , B Raf , C Raf ) are central players in cellular signal transduction , and thus often causally involved in the development of cancer when mutated or over expressed . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| B Raf and Raf 1 are regulated by distinct autoregulatory mechanisms . ^^^ However , unlike Raf 1 , the phosphorylation of B Raf at Ser ( 445 ) was constitutive and was only moderately increased by expression of constitutively active H Ras or constitutively active PAK 1 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| The Raf family of kinases has three members , Raf 1 , B Raf , and A Raf . ^^^ The ability of Raf 1 and B Raf to bind phosphatidylserine ( PS ) and phosphatidic acid ( PA ) has been show to facilitate Raf membrane associations and regulate Raf kinase activity . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Among the 92 interactors with known function were a number of proteins previously implicated in oncogenic signaling ( APC , A RAF , B RAF , and c RAF ) and cell cycle regulation ( AJUBA , c TAK , PTOV 1 , and WEE 1 ) . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| We showed that the effects of RKIP on B Raf functions were independent of its known inhibitory action on Raf 1 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| In mammals there are three isoforms , A RAF , B RAF and C RAF , and recently it was shown that the B RAF isoform is mutated in a high proportion of melanomas . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| To elucidate the importance of MAPK signaling in the development of advanced prostate cancer drug resistance , DU 145 and PC 3 prostate cells were stably infected / transfected with constitutively activated mutants of both Raf 1 and B Raf . ^^^ Results from MTT analyses suggested that activation of either Raf 1 or B Raf is inconsequential in prostate cancer chemoresistance . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Raf kinase inhibitory protein regulates Raf 1 but not B Raf kinase activation . ^^^ Because c Raf 1 and B Raf are both required for maximal MAPK stimulation by epidermal growth factor in neuronal and epithelial cell lines , we determined whether RKIP significantly affects MAPK signaling . ^^^ These results indicate that selective modulation of c Raf 1 but not B Raf activation by RKIP can limit the dynamic range of the MAPK signaling response to growth factors and may play a critical role in growth and development . . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| We examined the contributions of the small GTPases Rap and Ras and the serine threonine kinases B Raf and Raf 1 to the activation of these kinases in human islet cells . ^^^ METHODS : The expression of Rap , Ras , B Raf and Raf 1 in human islets was examined by immunohistochemistry and immunoblotting . ^^^ In these islets , the Rap B Raf signalling pathway was activated preferentially compared with Ras and Raf 1 , and activated Rap and B Raf mediated ERK stimulation in kinase assays in vitro . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
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 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Bag 1 is a cochaperone for the heat shock protein Hsp 70 that interacts with C Raf , B Raf , Akt , Bcl 2 , steroid hormone receptors and other proteins . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| This cell type specificity is explained in part by the finding that Rin binds and stimulates b Raf but does not activate c Raf . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| ERK MAP kinase signaling in post mortem brain of suicide subjects : differential regulation of upstream Raf kinases Raf 1 and B Raf . ^^^ The Raf kinases Raf 1 and B Raf are upstream activators of the extracellular signal regulated kinase ( ERK ) signaling pathway and therefore participates in many physiological functions in brain , including neuronal survival and synaptic plasticity . ^^^ The study was performed in prefrontal cortex ( PFC ) and hippocampus obtained from 28 suicide victims and 21 normal controls . mRNA levels of Raf 1 , B Raf , and cyclophilin were measured by quantitative RT PCR . ^^^ Protein levels of Raf 1 and B Raf were determined by Western blot , whereas their catalytic activities were determined by immunoprecipitation and enzymatic assays . ^^^ Our results of selective reduction in catalytic activity and expression of B Raf but not Raf 1 suggest that B Raf may be playing an important role in altered ERK signaling in brain of suicide subjects , and thus in the pathophysiology of suicide . . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| The three Raf family members , Raf 1 , B Raf , and A Raf , are highly homologous , and they are all expressed in the heart . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
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 ) . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| There are three RAF isoforms : ARAF , BRAF , and CRAF . ^^^ To determine the key RAF isoform mediating RET / PTC induced ERK phosphorylation , we stably transfected doxycycline inducible RET / PTC3 expressing thyroid PCCL 3 cells with small interfering RNA vectors to induce selective knockdown of BRAF or CRAF . ^^^ Conditional RET / PTC3 expression induced comparable ERK phosphorylation in CRAF knockdown and control cells but negligible ERK phosphorylation in BRAF knockdown cells . ^^^ |
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| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Conditionally active forms of the Raf proteins ( Raf 1 , B Raf , and A Raf ) were created by ligating NH 2 terminal truncated activated forms ( Delta ) to the estrogen receptor ( ER ) hormone binding domain resulting in estradiol regulated constructs ( DeltaRaf : ER ) . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| B Raf and C Raf signaling investigated in a simplified model of the mitogenic kinase cascade . ^^^ Picking the central Ras Raf MEK ERK signal cascade , we developed a mathematical model of how stimuli induce different signal patterns and thereby different cellular responses , depending on cell type and the ratio between B Raf and C Raf . ^^^ Based on biochemical data for activation and dephosphorylation , as well as the differential equations of our model , we suggest a different signaling pattern and response result for B Raf ( strong activation , sustained signal ) and C Raf ( steep activation , transient signal ) . ^^^ We further support the significance of such differential modulatory signaling by showing different Raf isoform expression in various cell lines and experimental testing of the predicted kinase activities in B Raf , C Raf and mutated versions . . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| In this study we have explored the expression , signaling and function of the three known Raf isoforms ( Raf 1 , A Raf and B Raf ) in patients with ovarian cancer . ^^^ While increased expression of Raf 1 was associated with poor survival , increased expression of B Raf was associated with improved survival . ^^^ Antisense inhibition of function in ovarian cancer cell lines indicated that both Raf 1 and A Raf , but not B Raf , were linked to cell proliferation . ^^^ Raf 1 ( but not A Raf or B Raf ) was also associated with reduced apoptosis . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Wild type and mutant B RAF activate C RAF through distinct mechanisms involving heterodimerization . ^^^ We examine the mechanism underlying C RAF activation by B RAF . ^^^ We show that wild type B RAF forms a complex with C RAF in a RAS dependent manner , whereas the mutants bind independently of RAS . ^^^ Importantly , we show that wild type B RAF can also activate C RAF . ^^^ Our data suggest that B RAF activates C RAF through a mechanism involving 14 3 3 mediated heterooligomerization and C RAF transphosphorylation . ^^^ |
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| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| We show that Raf 1 and A Raf require Hsp 90 for stability , whereas B Raf does not . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Ablation of the two best studied Raf kinases , B Raf and Raf 1 , is lethal at midgestation in mice , hampering the detailed study of the essential functions of these proteins . ^^^ B Raf deficient placentae show complete absence of phosphorylated ERK and strongly reduced HIF 1alpha and VEGF levels , whereas all these parameters are normal in Raf 1 deficient placentae . ^^^ |
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| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| B Raf and C Raf are required for Ras stimulated p 42 MAP kinase activation in Xenopus egg extracts . ^^^ We found that both B Raf and C Raf , but not Mos , are required for Ras induced MEK 1 and p 42 MAPK activation . ^^^ |
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| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| They were equally as sensitive to pharmacological inhibition of MEK1 / 2 for cell proliferation and transformation as ( V600E ) B Raf cells . siRNA mediated depletion of Raf 1 did not affect either ERK1 / 2 activation , whereas siRNA mediated depletion of B Raf reduced cell proliferation by up to 65 % through the inhibition of ERK1 / 2 activation , irrespective of the mutational status of B Raf . ^^^ |
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| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Regulation and role of Raf 1 / B Raf heterodimerization . ^^^ Raf 1 and B Raf can form heterodimers , and this may be important for cellular transformation . ^^^ Here , we have analyzed the biochemical and biological properties of Raf 1 / B Raf heterodimers . ^^^ Isolated Raf 1 / B Raf heterodimers possessed a highly increased kinase activity compared to the respective homodimers or monomers . ^^^ Heterodimers between wild type Raf 1 and B Raf mutants with low or no kinase activity still displayed elevated kinase activity , as did heterodimers between wild type B Raf and kinase negative Raf 1 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| PDE 3 but not PDE 4 inhibitors activate B Raf but not Raf 1 , as assessed by an in vitro kinase assay . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Mixed lineage kinase 3 regulates B Raf through maintenance of the B Raf / Raf 1 complex and inhibition by the NF 2 tumor suppressor protein . ^^^ B Raf and Raf 1 function within an oligomer wherein they are regulated in part by mutual transactivation . ^^^ Instead , MLK 3 is a component of the B Raf / Raf 1 complex and is required for maintenance of the integrity of this complex . ^^^ Finally , we demonstrate that merlin and MLK 3 can interact in situ and that merlin can disrupt the interactions between B Raf and Raf 1 or those between MLK 3 and either B Raf or Raf 1 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| In a screen of 82 acute myeloid leukemia ( AML ) samples , 45 ( 55 % ) showed activated ERK and thus were further analyzed for mutations in B RAF and C RAF . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| The recent demonstration of mutations in B RAF and C RAF in human tumors marked the return of RAF kinases to their roots as oncogenes . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Rheb inhibits C raf activity and B raf / C raf heterodimerization . ^^^ Here , we demonstrate for the first time that activation of Rheb is associated with decreased B Raf and C Raf phosphorylation at residues Ser 446 and Ser 338 , respectively , concomitant with a decrease in the activities of both kinases and decreased heterodimerization of B Raf and C Raf . ^^^ Importantly , the impact of Rheb on B Raf / C Raf heterodimerization and kinase activity are rapamycin insensitive , indicating that they are independent of Rheb activation of the mammalian target of rapamycin Raptor complex . ^^^ Taken together , these results support a central role of Rheb in the regulation of the Ras / B Raf / C Raf / MEK signaling network . . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Hsp 90 client proteins include telomerase , mutated p 53 , Bcr Abl , Raf 1 , Akt , HER2 / Neu ( ErbB 2 ) , mutated B Raf , mutated EGF receptor , and HIF 1alpha . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| By the use of probes based on the principle of fluorescence resonance energy transfer , we found that this amino terminal B Raf specific region is essential for homo dimerization of B Raf and hetero dimerization of B Raf and c Raf at the plasma membrane , followed by phosphorylation of Thr 118 in the amino terminal B Raf specific region . ^^^ HeLa cells expressing B Raf , but not c Raf , or a B Raf mutant lacking the B Raf specific region , showed enhanced MEK phosphorylation upon stimulation with a calcium agonist . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| It operates as part of a multichaperone complex and is essential for the conformation , stability , and function of several key oncogenic client proteins such as mutant p 53 , ERBB 2 , B RAF , C RAF , and CDK 4 . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| ERK and beyond : insights from B Raf and Raf 1 conditional knockouts . ^^^ Recently , we and others have generated mouse strains that allow the conditional ablation of the genes coding for Raf 1 , B Raf and MEK 1 . ^^^ Here , we discuss some of the surprises yielded by the analysis of the role of B Raf and Raf 1 and of their downstream effectors . . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| Raf kinase isoforms ( wild type Raf 1 or the b raf V600E oncogene ) are overactivated in a variety of solid tumor types , including renal cell carcinoma ( RCC ) , hepatocellular carcinoma ( HCC ) , non small cell lung cancer ( NSCLC ) , melanoma , and papillary thyroid carcinoma . ^^^ Sorafenib is the first oral multi kinase inhibitor to be developed that targets Raf kinases ( Raf 1 , wild type B Raf , and b raf V600E ) , in addition to receptor tyrosine kinases associated with angiogenesis ( vascular endothelial growth factor receptor [ VEGFR ] 2 / 3 , platelet derived growth factor receptor [ PDGFR ] beta ) or tumor progression ( Flt 3 , c kit ) . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| A Raf , B Raf and C Raf , the 3 mammalian members of the Raf family , are involved in a variety of cellular processes such as growth , proliferation , survival , differentiation and transformation . ^^^ |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: P15056 and P04049 |
Pubmed |
SVM Score :0.0 |
| NA |
|