Pubmed abstracts for Protein-Protein Interaction search result :


Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.98213445
Raf 1 forms a stable complex with Mek 1 and activates Mek 1 by serine phosphorylation . 0.98213445^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.970812
We further demonstrate in NIH3T3 and Rat 1a cells that Raf 1 is activated , as measured by its ability to phosphorylate MEK 1 , in response to epidermal growth factor but not thrombin . 0.970812^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.63763502
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 . 0.63763502^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.94037244
In addition , neither Mek 1 nor Mek 2 are stably activated in coordination with Raf 1 in nocodazole arrested cells . 0.94037244^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.6372073
The present study characterizes the interaction between the Raf 1 kinase domain and MEK 1 and examines whether the magnitude of their interaction correlates to the ability of Raf to phosphorylate MEK 1 . 0.6372073^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
When two additional subjects were studied using a one legged exercise protocol , MAPK phosphorylation and p 90 ribosomal S 6 kinase 2 , MAP kinase kinase 1 , and Raf 1 activities were increased only in the exercising leg . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Contraction resulted in a rapid and transient activation of Raf 1 and MAP kinase kinase 1 , a rapid and more sustained activation of MAP kinase and the 90 kDa ribosomal S 6 kinase 2 , and a dramatic increase in c fos mRNA expression . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
GnRH induced phosphorylation of MAPK / ERK kinase 1 and c Raf kinase was blocked by Cam inhibition , whereas activity of phospholipase C was unaffected , suggesting that Ca2+ / Cam modulation of the ERK cascade potentially at the level of c Raf kinase . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
The 5 Mos catalyzed phosphorylation sites on recombinant MAPKK 1 were identified by electrospray ionization mass spectrometry as S 218 and S 222 , located within a sequence that aligns with the T loop structure of cAMP dependent protein kinase ; these are the same as the Raf 1 phosphorylation site identified previously [ Alessi , D . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
PDGF BB also activated MAPK kinase 2 ( MAPKK 2 ) but had no effect on MAPKK 1 and Raf 1 activity . ^^^
Interacting proteins: Q02750 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: Q02750 and P04049 Pubmed SVM Score :0.0
The T cell antigen receptor utilizes Lck , Raf 1 , and MEK 1 for activating mitogen activated protein kinase . ^^^ Utilizing immunocomplex kinase assays , we demonstrated that TCR / CD3 ligation activated a MAP kinase kinase kinase ( Raf 1 ) as well as a MAP kinase kinase ( MEK 1 ) in Jurkat but not in J . ^^^ It was possible , however , to activate Raf 1 , MEK 1 , and p42MAPK in J . ^^^ These data show that the TCR activates MAP kinase by way of a signaling cascade , which depends upon Lck , and may be mediated by downstream events involving PKC or p95Vav which act on Raf 1 and MEK 1 . . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
The specific activity of the [ Asp 218 , Asp 222 ] and [ Asp 218 , Glu 222 ] Mek 1 mutants , 29 nanomole phosphate per minute per milligram , is similar to that of wild type Mek 1 activated by Raf 1 in vitro . ^^^ Although the mutants with double acidic substitutions could not be further activated by Raf 1 , three of those with single acidic substitution were activated by Raf 1 to the specific activity of activated wild type Mek 1 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Activation of MEK 1 by MEKK C is accompanied by phosphorylation of S 218 and S 222 , which are also phosphorylated by the protein kinases c Mos and Raf 1 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Inasmuch as hSOS is involved in p21ras activation , we also demonstrated that mIgM ligation activated a Ras dependent kinase cascade in which sequential activation of Raf 1 and MEK 1 culminates in the activation of p 42 mitogen activated protein ( MAP ) kinase ( ERK 2 ) . ^^^ The tumour promoter and protein kinase C agonist , phorbol 12 myristate 13 acetate ( PMA ) , also activated Raf 1 , MEK 1 , and MAP kinase in Ramos cells , but did not induce tyrosine phosphorylation of Shc or Shc / Grb2 association . ^^^ Okadaic acid , another tumour promoter and serine / threonine phosphatase inhibitor , activated p 42 MAP kinase without activating Raf 1 or MEK 1 , suggesting the existence of a serine / threonine phosphatase which directly regulates MAP kinase activity . . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Stimulation of these cells with Ag , carbachol , Ca ( 2+ ) ionophore , or thapsigargin resulted in the phosphorylation of Raf 1 , MEK 1 , p42mapk MAP kinase , and the recently cloned cytosolic phospholipase A 2 ( PLA 2 ) and increased activities of both MAP kinase and PLA 2 , as well as release of arachidonic acid . ^^^
Interacting proteins: Q02750 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 . ^^^ 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: Q02750 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: Q02750 and P04049 Pubmed SVM Score :0.0
Complexes containing products of the protooncogenes ras and raf 1 and the protein kinase MEK 1 activate the mitogen activated protein kinases ( MAPKs ) , which play a central role in the integration of different mitogenic signals by directly phosphorylating cytoplasmic and nuclear targets . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Involvement of Janus kinases , p52shc , Raf 1 , and MEK 1 in the IL 6 induced mitogen activated protein kinase cascade of a growth responsive B cell line . ^^^ Here we demonstrate the activation of Raf 1 and MEK 1 , which act as a MAP kinase kinase kinase and a MAP kinase kinase , respectively , in the MAP kinase cascade induced by IL 6 in AF 10 cells . ^^^ Although induction of tyrosine phosphorylation and activation of MAP kinase by IL 6 in a differentiation responsive B cell line , SKW 6 . 4 , were below the limits of detection , the phorbol ester PMA did activate Raf 1 , MEK 1 , and MAP kinase without inducing the phosphorylation of gp 130 , JAKs , or p52shc . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
RAS and RAF 1 form a signalling complex with MEK 1 but not MEK 2 . ^^^ Recent studies have demonstrated the existence of a physical complex containing p21ras ( RAS ) , p74raf 1 ( RAF 1 ) , and MEK 1 . ^^^ Complex formation among RAS , RAF 1 , and MEK 1 was dependent only on RAS : GMP PNP and not on cell stimulation . ^^^ Incubations of lysates with immobilized RAS depleted all RAF 1 from the lysate but bound only a small fraction of cytosolic MEK 1 , and further MEK 1 could bind immobilized RAS only if exogenous RAF 1 was added to the lysate . ^^^ This indicates that binding of MEK 1 to RAS depends on the presence of RAF 1 or an equivalent protein . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
An activator of MAP kinases , Mek 1 , phosphorylates MAP kinases at threonine and tyrosine residues and is itself phosphorylated at serine 218 and 222 by the protooncogene product Raf 1 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
B Raf and Raf 1 both efficiently phosphorylate MAP kinase kinase ( MEK 1 ) . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
In human MEK 1 , substitution of either serine residue 218 or 222 with alanine completely abolished its activation by epidermal growth factor stimulated Swiss 3T3 cell lysates or immunoprecipitated c raf , suggesting that both serine residues are required for MEK 1 activation . ^^^ Phosphopeptide analysis demonstrated that serine residues 218 and 222 of human MEK 1 are the primary sites for phosphorylation by c raf . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Active Raf 1 phosphorylates and activates the mitogen activated protein ( MAP ) kinase / extracellular signal regulated kinase kinase 1 ( MEK 1 ) , which in turn phosphorylates and activates the MAP kinases / extracellular signal regulated kinases , ERK 1 and ERK 2 . ^^^ Expression of constitutively active Raf 1 or MEK 1 in Jurkat T cells enhanced the stimulation of IL 2 promoter driven transcription stimulated by a calcium ionophore and PMA , and together with a calcium ionophore the expression of each protein was sufficient to stimulate NF AT activity . ^^^ Expression of MEK 1 interfering mutants inhibited the stimulation of IL 2 promoter driven transcription and blocked the ability of constitutively active Ras and Raf 1 to costimulate NF AT activity with a calcium ionophore . ^^^ Expression of the MAP kinase specific phosphatase , MKP 1 , which blocks ERK activation , inhibited IL 2 promoter and NF AT driven transcription stimulated by a calcium ionophore and PMA , and in addition , MKP 1 neutralized the transcriptional enhancement caused by active Raf 1 and MEK 1 expression . ^^^ We conclude that the MAP kinase signal transduction pathway consisting of Raf 1 , MEK 1 , and ERK 1 and ERK 2 functions in the stimulation IL 2 gene transcription in activated T lymphocytes . . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Interestingly , A Raf does not activate MEK 2 , although c Raf can activate both MEK 1 and MEK 2 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
However , the expression of a kinase deficient mitogen activated protein kinase kinase 1 ( MEK 1 ) did not prevent activation of the 92 kDa gelatinase B promoter by ras and a constitutively activated c raf expression vector was insufficient for 92 kDa gelatinase B promoter activation . ^^^
Interacting proteins: Q02750 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: Q02750 and P04049 Pubmed SVM Score :0.0
As a result , stimulation of HepG 2 cells that express the kinase inactive receptor leads to activation of serine / threonine kinases of the MAP kinase cascade which include RAF 1 , MEK 1 and p 42 MAP kinase . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Bombesin induced a marked and persistent activation of the mitogen activated protein kinase kinase 1 ( MEK 1 ) , p 42 ( mapk ) and p 90 ( rsk ) in Swiss 3T3 cells by a pathway that was independent of p 74 ( raf 1 ) but dependent on the activity of protein kinase C . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
OSM also induced the activation of ERK 2 by activating the serine / threonine kinases Raf 1 and [ mitogenactivated protein kinase ( MAPK ) ERK kinase ( MEK 1 ) ] 1 , while bFGF failed to activate any of the above components . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
In contrast , phosphorylation of Raf 1 , MEK 1 , p42mapk , and cytosolic phospholipase A 2 , as well as the associated increase in MAP kinase activity and release of arachidonic acid , were markedly inhibited in cells treated with as little as 10 nM dexamethasone a concentration that only partially inhibited hydrolysis of inositol phospholipids or release of secretory granules . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Interferon gamma and several other cytokines that are known to activate JAK 2 kinase were also found to stimulate Raf 1 kinase activity toward MEK 1 in mammalian cells . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Raf 1 , Raf B , Mek 1 , Mek kinase , and p 90 ( rsk ) kinases were also shown to be activated independently in a distinct time dependent pattern through the two Tnf receptors . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Mek 1 phosphorylation site mutants activate Raf 1 in NIH 3T3 cells . ^^^ Analysis of the Erk 1 pathway revealed Raf 1 activation , which correlated qualitatively with the MAP kinase activity seen in the [ Asp 218 ] and [ Asp 218 , Asp 222 ] Mek 1 infected clonal cell lines . ^^^ These data suggest that Mek 1 phosphorylation site mutants activate Raf 1 and MAP kinase by a Ras independent pathway and that the mechanism by which transformation occurs may utilize pathways that are MAP kinase independent . . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Together , our findings indicate that mKSR 1 is an integral component of the MAPK module functioning via a novel mechanism to modulate signal propagation between Raf 1 , MEK 1 , and MAPK . . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Interestingly , integrin mediated Erk 2 , Mek 1 , and Raf 1 activation , but not Ras GTP loading , was inhibited at least 80 % by wortmannin and LY 294002 . ^^^ We conclude that integrin mediated adhesion to fibronectin results in the accumulation of the PI 3 kinase products PI ( 3 , 4 ) P 2 and PI ( 3 , 4 , 5 ) P 3 as well as the PI 3 kinase dependent activation of the kinases Raf 1 , Mek 1 , Erk 2 , and AKT and that PI 3 kinase may function upstream of Raf 1 but downstream of Ras in integrin activation of Erk 2 MAP and AKT kinases . . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Our results indicate that : 1 ) STAT proteins play an essential role in angiotensin 2 induced vascular smooth muscle cell proliferation , 2 ) JAK 2 plays an essential role in the tyrosine phosphorylation of Raf 1 , and 3 ) convergent mitogenic signaling cascades involving the cytosolic kinases JAK 2 , MEK 1 , and ERK 1 mediate vascular smooth muscle cell proliferation in response to both growth factor and G protein coupled receptors . . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
PAK 1 phosphorylates MEK 1 on Ser 298 , a site important for binding of Raf 1 to MEK 1 in vivo . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
MEK 1 mediates a positive feedback on Raf 1 activity independently of Ras and Src . ^^^ This study shows that MEK 1 , the direct downstream effector of Raf 1 , can also stimulate Raf 1 kinase activity by a positive feedback loop . ^^^ Activated MEK 1 mediates hyperphosphorylation of the amino terminal regulatory as well as of the carboxy terminal catalytic domain of Raf 1 . ^^^ MEK 1 mediated Raf 1 activation is inhibited by co expression of the MAPK specific phosphatase MKP 1 indicating that the MEK 1 effect is exerted through a MAPK dependent pathway . ^^^ Stimulation of Raf 1 activity by MEK 1 is independent of Ras , Src and tyrosine phosphorylation of Raf 1 . ^^^
Interacting proteins: Q02750 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: Q02750 and P04049 Pubmed SVM Score :0.0
In light of recently published data , we propose that a positive signal initiated following oligomerization of CD 4 by the virus is likely to involve a recruitment of active forms of p 56 ( lck ) , Raf 1 , MEK 1 , and ERK 1 , before AP 1 and NF kappa B activation . . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Activation of Raf 1 and MEK 1 , upstream kinases of ERK 1 , was shown by increased Raf 1 kinase activity in anti Raf 1 immunoprecipitates of OLG treated with C5b 9 and ERK 1 activity that can be inhibited by PD 098 , 059 , a specific MEK 1 inhibitor . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
ERK 2 is activated via a kinase cascade initiated by activation of the G protein p21Ras followed by phosphorylation and activation of Raf 1 and mitogen activated protein kinase kinase 1 ( MEK 1 ) . ^^^ In the present paper , we studied in human primary T cells the possible involvement of the Raf 1 / MEK 1 / ERK 2 pathway upon stimulation by jacalin , a mitogenic lectin which specifically stimulates CD4+ lymphocytes . ^^^ This shows , as already suggested , that another pathway in addition to the Raf 1 / MEK 1 / ERK 2 kinase cascade could be triggered in T cell activation . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Hydrogen peroxide activates extracellular signal regulated kinase via protein kinase C , Raf 1 , and MEK 1 . ^^^ In addition , H2O2 treatment significantly increased both MEK 1 and Raf 1 activity . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Mitogens induce the sequential activation of the kinases Raf 1 > Mek 1 > Erk 2 > Rsk via the G protein Ras . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Two lines of evidence suggest that the MAPK cascade induces the activity of MyoD : 1 ) the expression of constitutively activated forms of MEK 1 or Raf 1 enhanced the transcriptional activity of MyoD in 10T1 / 2 fibroblasts ; and 2 ) the addition of PD 098059 to fibroblast cells expressing a conditional MyoD estrogen fusion protein significantly inhibited the expression of MyoD responsive genes . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Interaction of the Grb 10 adapter protein with the Raf 1 and MEK 1 kinases . ^^^ We show that this unusual SH 2 domain interacts , in a phosphotyrosine independent manner , with both the Raf 1 and MEK 1 kinases . ^^^ Interaction of Grb 10 with Raf 1 is constitutive , while interaction between Grb 10 and MEK 1 needs insulin treatment of the cells and follows mitogen activated protein kinase activation . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Our previous results have demonstrated that Shc , Erk 1 and Mek 1 mRNAs are up regulated during nerve regeneration , whereas PKA which inhibits the Ras Erk pathway via Raf 1 was down regulated . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Raf 1 activity , measured by phosphorylation of Mek 1 , was attenuated by the addition of PGE 2 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Deletion of the insert had no effect on either the activity of MEK 1 or on its ability to bind to Raf 1 . ^^^ Both wild type and constitutively active MEK 1 coimmunoprecipitated with Raf 1 whether or not the insert was present . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Furthermore , we show that PKC activation of the cytoplasmic kinase cascade ( Raf 1 kinase , MAP kinase kinase [ MEK 1 ] , and extracellular signal regulated kinase [ ERK 1 ] ) by o HA culminated in the nuclear translocation of ERK 1 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
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 . ^^^ Additionally , both PGF2alpha ( 1 microM ) and PMA ( 20 nM ) stimulated phosphorylation of Raf 1 , MEK 1 , and p42mapk in 32P labeled cells . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Most of the mitogenic protein kinases including Raf 1 , RafB , Mek 1 , Erk 2 , and Rsk 1 were significantly down regulated , whereas the stress signaling kinases , such as Mlk 3 , Mekkl , Sekl , Mkk 3 , and Mapkapk 2 were up regulated in expression during postnatal development . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Ceramide signaled apoptosis in BAD expressing cells by a pathway involving sequentially kinase suppressor of Ras ( KSR ) / ceramide activated protein kinase , Ras , c Raf 1 , and MEK 1 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Both IL 8 and GROalpha activate ERK and MEK through R 2 , whereas MIP 1alpha , a beta chemokine , does not activate these kinases through either of these receptors . ( b ) ERK activation is inhibited by pertussis toxin and MEK 1 inhibitor . ( c ) ERK activation is independent of the upstream mediators Ras and Raf 1 . ( d ) The downstream effects of ERK activation result in an increase of c fos mRNA through both R 1 and R 2 receptors . . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
In contrast , epidermal growth factor ( EGF ) induced luciferase activity , which is independent of PKC activation ( Ras > Raf 1 > MEK 1 > MAP kinases > GAL 4 Elk1 phosphorylation > luciferase expression > luciferase activity ) can only be blocked using a selective EGF receptor inhibitor ( AG 1478 ) . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
TPO did not activate the mitogen activated protein kinase / ERK kinases , MEK 1 and MEK 2 , but activated Raf 1 and directly augmented the PKC mediated MEK activation , suggesting that TPO primarily potentiates the ERK pathway through regulating MEKs or upstream steps of MEKs including Raf 1 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
In vitro , however , SB 203580 stimulated Raf 1 activates MEK 1 in a coupled assay . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Removal of extracellular Ca2+ ( by EGTA ) or blockade of L type Ca2+ channels ( by nifedipine ) , as well as inhibition of MEK 1 kinase ( by PD 98059 ) , enhanced Raf 1 activity , whereas wortmannin ( 100 nM ) inhibited approximately one half of Ang 2 stimulated Raf 1 activity . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Cotransfection of the myocytes with constitutively active versions of Ras and MEK 1 or an estrogen inducible version of Raf 1 also stimulated transcription from the Glut 1 promoter . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
To identify Raf 1 independent upstream signaling intermediates of mitogen activated protein kinase / ERK kinase 1 ( MEK 1 ) , the dual function kinase required and sufficient for ERK activation in these cells , lysates from forskolin and PDGF treated bovine tracheal myocytes were resolved using ion exchange chromatography . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
However , inhibition of mitogen activated protein kinase with PD 098059 did not preclude apoptosis and in fact increased the rate of apoptosis observed in serum deprived Ha ras transformed cells , indicating that the Ras / Raf 1 pathway induced apoptosis throughout a mitogen activated protein kinase kinase 1 ( MEK 1 ) independent pathway . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Raf 1 phosphorylates and activates MEK 1 , a kinase that activates the extracellular signal regulated kinases ( ERK ) . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Although JSAP 1 coprecipitated with MEK 1 MAPKK and Raf 1 MAPKKK , and not MKK 6 or MKK 7 MAPKK , in cotransfected COS 7 cells , MEK 1 and Raf 1 do not interfere with the binding of SEK 1 and MEKK 1 to JSAP 1 , respectively . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
We examined the importance of this binding site in the feedback phosphorylation of MEK 1 on Thr ( 292 ) and Thr ( 386 ) by ERK 2 , the phosphorylation and activation of ERK 2 by MEK 1 , and the interaction of MEK 1 with ERK 2 and Raf 1 . ^^^ Deletion of the N terminal ERK binding domain of MEK 1 also reduced its ability to phosphorylate ERK 2 in vitro , to co immunoprecipitate with ERK 2 , and to stimulate ERK 2 activation in transfected cells , but it did not alter the association with endogenous Raf 1 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Transduction of kinase defective dominant negative c raf mutant or application of PD 098059 , a specific inhibitor of MEK 1 , also abrogates the G 1 cell cycle arrest in cells with disintegrated microtubule system . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Moreover , the activity of Raf 1 and MEK 1 protein kinases , the activators upstream MAPK in the phosphorylation cascade induced by EGF , was not modified in 8 Cl cAMP treated cells . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
We have recently demonstrated that the Grb 10 SH2 domain interacts with both the Raf 1 and MEK 1 kinases . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
In contrast , H ( 2 ) O ( 2 ) induced ERK activation is dependent on EGFR activation , which then leads to downstream Raf 1 and MEK 1 activation . . ^^^
Interacting proteins: Q02750 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: Q02750 and P04049 Pubmed SVM Score :0.0
Co transfection of NIH 3T3 fibroblasts with human decorin promoter / chloramphenicol acetyltransferase ( CAT ) construct ( pDEC 879 / CAT ) in combination with the expression vectors for constitutively active Raf 1 and MEK 1 markedly suppressed decorin promoter activity . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Serum starved cells and cells grown in medium with serum did not show constitutively activated c Raf , MEK 1 , or p 42 MAPK . ^^^ Stimulation of cells with epidermal growth factor ( EGF ) or fetal calf serum ( FCS ) resulted in activation of N Ras , but not K Ras , as well as activation of c Raf , MEK 1 , and p 42 MAPK . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
This same pattern in both cells of IRS 1 dependent augmentation and IRS 1 independent wortmannin sensitivity was also observed for GH induced activation of Akt and MEK 1 ( using state specific antibody blotting for both ) , despite the lack of difference in GHR , JAK 2 , SHP 2 , p 85 , Akt , Ras , Raf 1 , MEK 1 , ERK 1 , or ERK 2 abundance between the two cells . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
In this study we demonstrate that endogenous MEKK 1 binds to endogenous ERK 2 , MEK 1 , and another MEKK level kinase , Raf 1 , suggesting that it can assemble all three proteins of the ERK 2 MAP kinase module . . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
To examine the possibility that there is bifurcation at the level of Raf in activation of MEK1 / 2 dependent and MEK1 / 2 independent cell regulatory events , we engineered a kinase active Raf 1 variant ( RafBXB ( T481A ) ) with an amino acid substitution that disrupts MEK 1 binding . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
In this report , we demonstrate a novel single step assay for Raf 1 kinase activity based on phosphorylation of recombinant MEK 1 , detected using an activation specific MEK antibody that recognizes MEK only when specifically phosphorylated by Raf 1 on Ser 217 and Ser 221 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
In that study we also found MEK 1 and Raf 1 , which are involved in the extracellular signal regulated kinase ( ERK ) MAPK cascades , bind to JSAP 1 . ^^^ Here we have defined the regions of JSAP 1 responsible for the interactions with MEK 1 and Raf 1 . ^^^ Finally , we investigated the molecular mechanism of JSAP 1 ' s inhibitory function and showed that JSAP 1 prevents MEK 1 phosphorylation and activation by Raf 1 , resulting in the suppression of the activation of ERK . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
The colony forming ability of NIH 3T3 cells overexpressing 14 3 3 beta in soft agar medium was efficiently abolished by exogenous expression of a dominant negative mutant of MEK 1 and 14 3 3 beta physically interacted with Raf 1 in these cells . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Ceramide activated protein kinases , such as the kinase suppressor of Ras ( KSR ) and protein kinase Czeta ( PKCzeta ) , are involved in the regulation of c Raf , which promotes sequential activation of MEK 1 and p42 / p44 MAPK in mammalian cells . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
The present study examined the phosphorylation states of components in the MAPK cascade , Raf 1 , MEK 1 , and extracellular signal regulated kinases ( ERKs ) , which are activated by mitogens , throughout early mouse embryo development and in cultured somatic cells generally . ^^^ In somatic cells , Raf 1 and MEK 1 were phosphorylated at M phase and dephosphorylated during interphase . ^^^ In contrast , after the four cell stage , not only ERKs , but also Raf 1 and MEK 1 , were not phosphorylated at any stage during the cell cycle in mouse early embryos . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Here , we show that both HCV genotype 1a and 3 core proteins activate MEK 1 and Erk1 / 2 MAP kinases and that the costitutive expression of the HCV core results in a high basal activity of Raf 1 and MAP / kinase / kinase , as determined by endogenous Raf 1 in vitro kinase assay and immunodetection of hyperphosphorylated Erk 1 and Erk 2 even after a serum starvation . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Further analyses disclosed that transfection of dominant negative forms of raf 1 , MEK 1 , ERK 1 , ERK 2 , or wild type MEKK 1 all increased cystatin A promoter activity in normal human keratinocytes , whereas wild type raf 1 , ERK 1 , ERK 2 , or dominant negative forms of MEKK 1 , MKK 7 , or JNK 1 suppressed the promoter activity . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
We report here that the activity of kinase suppressor of ras ( KSR 1 ) , a kinase upstream of raf 1 , is inhibited by both these compounds at concentrations similar to those that inhibit MEK 1 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
EGCG did not affect protein levels or the activity of Raf 1 significantly but decreased its association with MEK 1 as determined by co immunoprecipitation . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Here we show that GPIb 9 mediated activation of integrin alpha ( IIb ) beta ( 3 ) is inhibited by dominant negative mutants of Raf 1 and MEK 1 in a reconstituted integrin activation model in Chinese hamster ovary ( CHO ) cells and that the integrin dependent platelet aggregation induced by either vWF or low dose thrombin is inhibited by MEK inhibitors PD 98059 and U 0126 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
In addition , the GADD 45 promoter is strongly activated following expression of JNK 1 ; Raf 1 , which is an upstream activator of the ERK pathway ; or MEK 1 , an upstream activator of both the ERK and the JNK pathways . ^^^
Interacting proteins: Q02750 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: Q02750 and P04049 Pubmed SVM Score :0.0
Furthermore , tyrosine phosphorylation of FAK and phosphotyrosine kinase ( Pyk ) 2 ; serine phosphorylation of c Raf , MEK 1 , and Elk 1 ; and tyrosine threonine phosphorylation of Erk 1 and 2 were time dependently activated in the presence of GDNF . ^^^ More specifically , the Ras inhibitor manumycin inhibited phosphorylation of c Raf , MEK 1 , Erk 1 and 2 , and Elk 1 , but not that of FAK . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Activation of Raf 1 and MEK 1 was coincident with Erk activation . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
RKIP inhibits the phosphorylation of MAP / extracellular signal regulated kinase 1 ( MEK 1 ) by Raf 1 by disrupting the interaction between these two kinases . ^^^ This mode of action bears striking similarities to the interactions of RKIP with Raf 1 and MEK 1 in the MAPK pathway . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
By either conditionally reducing Raf 1 activity or completely disrupting the Raf 1 signaling by PD 98059 , a specific inhibitor of MEK 1 , the otherwise inhibited cytokine responses can be restored . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
We used three different inhibitors of phosphorylation pathways : 2 ' amino 3 ' methoxyflavone ( PD 098059 ) , a selective inhibitor of MEK 1 activator and the MAPK cascade ; 4 ( 4 fluorophenyl ) 2 ( 4 methylsulfinylphenyl ) 5 ( 4 pyridyl ) 1H imidazole ( SB 203580 ) , a specific inhibitor of the p 38 pathway ; and 7beta acetoxy 1alpha , 6beta , 9alpha trihydroxy 8 , 13 epoxy labd 14 en 11 one ( forskolin ) , an inhibitor at the level of Raf 1 kinase . ^^^
Interacting proteins: Q02750 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: Q02750 and P04049 Pubmed SVM Score :0.0
PAK 1 primes MEK 1 for phosphorylation by Raf 1 kinase during cross cascade activation of the ERK pathway . ^^^ These changes regulate the ability of Raf 1 to phosphorylate its downstream targets MEK 1 and MEK 2 . ^^^ Here we show that both Raf 1 and MEK 1 are phosphorylated by PAK 1 and that mutations at PAK 1 phosphorylation sites in either protein prevent cross cascade activation . ^^^ In contrast , MEK 1 activation by constitutively active Raf 1 is refractory to mutations at PAK 1 phosphorylation sites . ^^^ Phosphorylation of MEK 1 on serine 298 does not appear to regulate the interaction between Raf 1 and MEK 1 , but rather the ability of Raf 1 to phosphorylate MEK 1 with which it is complexed in vivo . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Co transfection of the MAO B promoter with dominant negative forms of Ras , Raf 1 , MEKK 1 , MEK 1 , MEK 3 , MEK 7 , ERK 2 , JNK 1 , and p38 / RK inhibit the PMA dependent activation of the MAO B promoter . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Overexpression of activated forms of c Raf and MEK 1 ( a component of the mitogen activated protein kinase pathway , MAPK ) led to cell dissociation , as inferred by the loss of desmosomes from the cell periphery . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Using mutant cells , chemical inhibitors , and specific dominant negative inhibitors , we show that induction of GATE driven gene expression depends on MEK 1 ( mitogen activated protein kinase kinase / extracellular signal regulated protein kinase kinase ) and ERKs ( extracellular signal regulated protein kinases ) but is independent of Raf 1 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
In NF kappaB luciferase reporter assays , we demonstrated complete inhibition of RLX induced NF kappaB activation in cells transfected with dominant negative Raf 1 , MEK 1 , or ERK 1 / 2 constructs , whereas dominant negative Ras had no effect . ^^^ In conclusion , RLX stimulates endothelial and epithelial ET ( B ) via a Ras independent Raf 1 MEK 1 ERK 1 / 2 pathway that activates NF kappaB . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
However , H ( 2 ) O ( 2 ) exhibited no effect on the activity of Raf 1 kinase , which was an upstream activator of MEK 1 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Baicalein inhibits Raf 1 mediated phosphorylation of MEK 1 in C 6 rat glioma cells . ^^^ To examine the site of action of baicalein , MEK 1 and Raf 1 were prepared by immunoprecipitation with anti MEK 1 and anti Raf 1 antibodies , respectively . ^^^ Baicalein inhibited the phosphorylation of exogenous MEK 1 by Raf 1 under cell free conditions , while it did not change the phosphorylation of exogenous p 42 MAPK by MEK 1 . ^^^ These results imply that baicalein inhibits the ERK / MAPK cascade , acting on the phosphorylation of MEK 1 by Raf 1 . . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Transfection of the dominant active form of Raf 1 ( Ad daRaf 1 ) or MEK 1 ( Ad daMEK 1 ) inhibited 1 , 25 ( OH ) ( 2 ) D 3 dependent cystatin A promoter activity and its expression . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
RAF 1 activated MEK 1 is found on the Golgi apparatus in late prophase and is required for Golgi complex fragmentation in mitosis . ^^^ MEK 1 dependent Golgi complex fragmentation is through activation by RAF 1 and not MEK 1 kinase 1 . ^^^ We propose that a RAF 1 dependent activation of MEK 1 and its presence on the Golgi apparatus in late prophase is required for Golgi complex fragmentation . . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Here , we show that basic fibroblast growth factor ( bFGF ) and vascular endothelial growth factor ( VEGF ) differentially activate Raf , resulting in protection from distinct pathways of apoptosis in human endothelial cells and chick embryo vasculature . bFGF activated Raf 1 via p 21 activated protein kinase 1 ( PAK 1 ) phosphorylation of serines 338 and 339 , resulting in Raf 1 mitochondrial translocation and endothelial cell protection from the intrinsic pathway of apoptosis , independent of the mitogen activated protein kinase kinase 1 ( MEK 1 ) . ^^^ In contrast , VEGF activated Raf 1 via Src kinase , leading to phosphorylation of tyrosines 340 and 341 and MEK 1 dependent protection from extrinsic mediated apoptosis . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Whereas CaMK inhibition affected neither integrin stimulated Akt phosphorylation nor p21Ras or Mek 1 activity , it was necessary for Raf 1 activity . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Signalling from Ras to AP 1 is through the Raf / MEK [ mitogen activated protein ( MAP ) kinase kinase ] / ERK ( extracellular signal regulated kinase ) MAP kinase pathway as sustained activation of Raf 1 or Mek 1 modifies AP 1 composition and activity . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
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: Q02750 and P04049 Pubmed SVM Score :0.0
METHODS : Paraffin sections of 10 tooth germs and 46 benign and 6 malignant ameloblastomas were examined immunohistochemically for the expression of K Ras , Raf 1 , MEK 1 , and ERK1 / 2 . ^^^ RESULTS : Immunohistochemical reactivity for K Ras , Raf 1 , MEK 1 , and ERK1 / 2 was detected in both normal and neoplastic odontogenic epithelium , and these molecules were reactive chiefly with odontogenic epithelial cells neighboring the basement membrane . ^^^ Conclusion : Expression of K Ras , Raf 1 , MEK 1 , and ERK1 / 2 in tooth germs and ameloblastomas suggests that Ras / MAPK signaling pathway functions to regulate cell proliferation and differentiation in both normal and neoplastic odontogenic epithelium . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Its expression in tumor cells is further enhanced upon tumor necrosis factor ( TNF ) alpha treatment , whereas hPEBP 4 normally co localizes with lysosomes , TNFalpha stimulation triggers its transfer to the cell membrane , where it binds to Raf 1 and MEK 1 . ^^^ Co precipitation and in vitro protein binding assay demonstrated that hPEBP 4 interacts with Raf 1 and MEK 1 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Interestingly , a subtle transition from maternal MAPK function to zygotic function was suggested by the localization for three MAPK pathway enzymes between E2 . 5 and E3 . 5 , Raf 1 phospho is largely cell membrane localized at E2 . 5 and E3 . 5 , and MEK 1 , 2 phospho accumulates in the nucleus on E2 . 5 and E3 . 5 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Insulin receptor , insulin receptor substrate 1 , Raf 1 , and Mek 1 during hormonal hepatocarcinogenesis by intrahepatic pancreatic islet transplantation in diabetic rats . ^^^ Thus , we investigated FAHs , HCAs , and HCCs for altered expression of insulin receptor , insulin receptor substrate 1 ( IRS 1 ) , Raf 1 and Mek 1 . ^^^ IRS 1 , Raf 1 , and Mek 1 proteins were strongly overexpressed in FAHs and tumors , as compared with the unaltered liver tissue . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
ALI enhanced expression of the following growth , invasion , and motility related molecules in the cells with or without hypoxia more greatly than SMC : c Met , Ras , mitogen activated protein kinase cascade proteins ( Raf 1 , MEK 1 , and ERK 1 / 2 ) , matrix metalloproteinase 1 , and filamin A . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Expression of Raf 1 and MEK 1 was also found to be significant , as determined by intensity analysis . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Thus , peroxynitrite activates ERK in cardiomyocytes through an unusual signaling cascade involving Raf 1 and MEK 1 , independently from EGFR and P 21 ( Ras ) , and also acts as a potent activator of JNK and p 38 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Moreover , we have observed that Raf 1 phosphorylation that occurs during meiosis resumption was dependent upon the activity of MEK 1 or Xp 42 ( Mpk 1 ) but not p 90 ( Rsk ) . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
The purified pseudopodial fraction contains phosphotyrosinated proteins , including Met and FAK , and various signaling proteins , including Raf 1 , MEK 1 , ERK 2 , PKBalpha ( Akt 1 ) , GSK3alpha , GSK3beta , Rb , and Stat 3 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Here , we focus on the group A p 21 activated kinases ( Paks ) , which have previously been implicated in regulating both c Raf and Mek 1 activity , by phosphorylating these proteins at Ser ( 338 ) and Ser ( 298 ) , respectively . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
We found that both B Raf and C Raf , but not Mos , are required for Ras induced MEK 1 and p 42 MAPK activation . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
After low number islet transplantation ( n = 450 ) , the liver acini downstream of the islets show insulin induced alterations : massive glycogen and / or fat accumulation , translocation of the insulin receptor , decrease in glucose 6 phosphatase activity , increase in expression of insulin like growth factor ( IGF ) 1 , IGF II / mannose 6 phosphate receptor , insulin receptor substrate 1 , Raf 1 , and Mek 1 , corresponding to clear cell preneoplastic foci of altered hepatocytes known from chemical hepatocarcinogenesis and identical to that in streptozotocin diabetic Lewis rats . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
During the next 12 24 months , many peri insular ductules progressed via tumor like cystic lesions to large cystic cholangiomas , accompanied by a translocation of the insulin receptor into the cytoplasm and an increase in expression of insulin related signaling proteins ( Insulin receptor substrate 1 , Raf 1 , Mek 1 ) . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
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 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
We found that endogenous hPEBP 4 interacts with Raf 1 and MEK 1 in TRAIL treated CaoV 3 cells by co immunoprecipitation analysis . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
For this purpose , hamster preantral follicles were cultured with FSH or EGF in the presence of selective kinase inhibitors FSH or EGF phosphorylated RAF 1 , MAP2K1 , and MAPK3 / 1 . ^^^ Sustained activation of MAPK3 / 1 beyond 3 h was independent of EGFR kinase activity but dependent on PKC activity , which appeared to form a self sustaining MAPK3 / 1 activation loop by activating RAF 1 , MAP2K1 , and PLA2G4 ( phospholipase A 2 [ all cytosolic isozymes ] ) . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Co infection of Sf 9 cells with either MKK 1 or MKK 2 virus together with recombinant viruses for Raf 1 , pp60src ( Y527F ) and c Ha Ras resulted in activations of 250 fold and 150 fold for MKK 1 and MKK 2 respectively . ^^^ Raf 1 phosphorylated MKK 1 on one major tryptic phosphopeptide , the phosphorylation of which increased with time . ^^^ Phosphorylation of MKK 1 by Raf 1 correlated with activation and reached a plateau of approximately 2 mol / mol . . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Moreover , the use of a CCL 39 derived cell line that stably expresses an inducible chimera of the estrogen receptor fused to a constitutively active Raf 1 mutant ( DeltaRaf 1 : ER ) revealed that in absence of growth factors , activation of the Raf > MKK 1 > p42 / p44MAPK cascade is sufficient to fully induce cyclin D 1 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Furthermore , the use of a CCL 39 derived cell line expressing an estradiol regulated form of oncogenic Raf 1 ( CCL 39 deltaRaf 1 : ER ) revealed that the exclusive activation of the Raf > MKK 1 > p42 / p44 MAPK cascade was capable of inducing NHE 1 activation to the same extent as potent growth factors like thrombin . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Raf 1 , a direct regulator of MKK 1 and MKK 2 , was activated under these conditions , and a synergistic activation of MKK was observed upon coexpression of Raf 1 and MKP 1 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
The induction of VEGF mRNA in response to conditioned activation of Raf 1 is reverted by an inhibitor of MKK 1 , PD 098059 , highlighting a specific role for the p42 / p44 MAP kinase pathway in VEGF expression . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
Paradoxically , exposure of cells to ZM 336372 induces > 100 fold activation of c Raf ( measured in the absence of compound ) , but without triggering any activation of MKK 1 or p 42 MAPK / ERK2 . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
ERK activation in response to constitutively active Raf 1 or growth factor stimulus was attenuated in cells expressing MKK 1 C terminal deletion mutants . ^^^ This could be partly explained by the inability of Raf 1 to phosphorylate MKK 1 C terminal deletion mutants even though the phosphorylation sites were intact in these mutants . ^^^
Interacting proteins: Q02750 and P04049 Pubmed SVM Score :0.0
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