| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| MEK 5 is the upstream BMK 1 kinase and exists as naturally occurring splice variants , MEK5alpha and MEK5beta . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| We have identified two components of a new protein kinase signaling cascade , MAPK / ERK kinase 5 ( MEK 5 ) and extracellular signal regulated kinase 5 ( ERK 5 ) . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Here we identify the evolutionarily conserved mitogen activated protein kinase kinase 5 ( MEK 5 ) extracellular signal regulated kinase 5 ( ERK 5 ) pathway as an essential regulator in neural differentiation . ^^^ |
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| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| The formation of the MEK5 / extracellular signal regulated kinase 5 ( ERK 5 ) complex is critical for MEK 5 to activate ERK 5 , to increase transcription via MEF 2 , and to enhance cellular survival in response to osmotic stress . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| MEKK 2 , MEK 5 , and extracellular signal regulated kinase 5 ( ERK 5 ) are members of a three kinase cascade for the activation of ERK 5 . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Additionally , we demonstrated that these GPCRs can elevate the activity of novel members of the MAPK family , including ERK 5 , p38alpha , p38gamma , and p38delta , and that the activation of certain kinases acting downstream from MEK 5 ( ERK 5 ) and MKK 6 ( p38alpha and p38gamma ) is necessary to fully activate the c jun promoter . ^^^ |
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| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| The reporter assays demonstrated that the serum induced enhancement of transcription from serum response element was significantly inhibited by expression of a dominant negative form of MEK 5 , which was a direct and specific activator for ERK 5 and that transcription from serum response element mediated by the Ets domain transcription factor Sap1a , but not by Elk 1 , was stimulated by coexpression of ERK 5 and active MEK 5 . ^^^ |
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| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| We have previously demonstrated an involvement of MEK 5 and ERK 5 in RafBXB stimulated focus formation in NIH3T3 cells . ^^^ We find here that MEK 5 and ERK 5 cooperate with the RafBXB effectors MEK1 / 2 and ERK1 / 2 to induce foci . ^^^ Consistent with results from our focus formation assays , constitutively active variants of MEK 5 and MEK 1 synergize to activate NF kappaB , and MEK 5 and ERK 5 are required for activation of NF kappaB by RafBXB . ^^^ Our results support the hypothesis that NF kappaB and p 90 ribosomal S 6 kinase are involved in MEK 5 ERK5 dependent focus formation and may serve as integration points for ERK 5 and ERK1 / 2 signaling . . ^^^ |
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| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| The MEK 5 extracellular signal regulated kinase ( ERK 5 ) tandem is a novel mitogen activated protein kinase cassette critically involved in mitogenic activation by the epidermal growth factor ( EGF ) . ^^^ Consistent with the role of the aPKCs in the MEK 5 ERK5 pathway , we show that zetaPKC and lambda / iotaPKC activate the Jun promoter through the MEF2C element , a well established target of ERK 5 . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| BDNF stimulation of ERK 5 required the activity of MEK 5 . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Targeted deletion of mek 5 causes early embryonic death and defects in the extracellular signal regulated kinase 5 / myocyte enhancer factor 2 cell survival pathway . ^^^ Further studies with mek 5 ( / ) MEFs indicate that MEK 5 is required for mediating extracellular signal regulated kinase 5 ( ERK 5 ) activation and for the regulation of the transcriptional activity of myocyte enhancer factor 2 . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Mutagenesis of Ets 1 ( T38A ) reduced CYP 24 promoter activity to levels observed with the dominant negative MEK 5 ( A ) and inhibited ERK 5 directed phosphorylation . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Consistent with this , a mutant form of MEK 5 , an upstream activator of ERK 5 , strongly suppressed PMA inducible promoter activity . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| This study used gene expression profiling analysis to identify and implicate mitogen activated protein kinase kinase ( MEK 5 ) BMK 1 ( big mitogen activated kinase 1 ) / extracellular signal related protein kinase ( ERK 5 ) pathway as a novel target involved in chemoresistance . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| MEK 5 is a specific activator of ERK 5 . c Fos and Fra 1 , well known immediate early gene products , are members of the AP 1 family . ^^^ Phosphorylation of c Fos appears to be mediated by ERK 5 and a kinase ( s ) lying downstream of ERK 5 , and the MEK 5 ERK5 pathway dependent phosphorylation sites on c Fos are different from the ERK1 / 2 pathway dependent ones . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Select point mutations in subdomain 10 impair MEKK 2 phosphorylation of the MAP2Ks , MKK 7 and MEK 5 , abolish MEKK 2 induced activation of the MAPKs , JNK 1 and ERK 5 , and diminish MEKK 2 dependent activation of an AP 1 reporter gene . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| PB 1 domains of MEKK 2 and MEKK 3 interact with the MEK 5 PB1 domain for activation of the ERK 5 pathway . ^^^ MEKK 2 and MEKK 3 are MAPK kinase kinases that activate the ERK 5 pathway by phosphorylating and activating the MAPK kinase , MEK 5 . ^^^ Activated MEK 5 then phosphorylates and activates ERK 5 . ^^^ Herein , we analyze the functional role of MEKK 2 , MEKK 3 , and MEK 5 PB1 domains in the ERK 5 activation pathway . ^^^ Expression in cells of the MEKK 2 or MEKK 3 PB1 domain inhibits ERK 5 activation , whereas expression of a mutant MEKK 2 unable to bind the MEK 5 PB1 domain or expression of the p67phox PB 1 domain has no effect on ERK 5 activation . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Overexpression of constitutively active MEK 5 and wt ERK 5 induces a cyclin D 1 reporter gene ( D 1 973 luciferase ) at least as well as constitutively active MEK 1 . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Inhibition of ERK 5 , MEK 5 activation or activation of MEKK 2 deficient mast cells was associated with inhibition of MEF2C phosphorylation and a decrease in c Jun expression . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| We show here that Erk 5 , a novel member of the MAPK family , and its specific upstream activator MEK 5 were activated in response to incubation of cells with G CSF . ^^^ In contrast , inhibition of protein kinase C activity increased G CSF mediated activation of Erk 5 and MEK 5 , whereas stimulation of protein kinase C activity inhibited activation of the two kinases by G CSF . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| The MAPK kinase MEK 5 activates the MAPK ERK 5 . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Since ERK 5 and its upstream activator MEK 5 are abundant in skeletal muscle we examined a function of the cascade during muscle differentiation . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Dendritic growth was also increased in cells transfected with dominant negative mutants of MEK 1 and ERK 2 but not with dominant negative mutants of MEK 5 and ERK 5 , suggesting that ERK1 / 2 is the primary mediator of this effect . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| MEK 5 and ERK 5 are localized in the nuclei of resting as well as stimulated cells , while MEKK 2 translocates from the cytosol to the nucleus upon stimulation . ^^^ The ERK 5 signaling cascade acts through sequential activation of MEKK2 / 3 , MEK 5 and ERK 5 and transmits signals to a variety of stress and mitogenic related targets . ^^^ ERK 5 remains bound to these nuclear moieties even after stimulation , while MEK 5 is detached from the anchors but remains localized in the nucleus . ^^^ Unlike ERK 5 and MEK 5 , their upstream activator MEKK 2 is localized mainly in the cytosol of resting cells , and translocates into the nucleus upon EGF stimulation , allowing transmission of signals to the nuclear MEK 5 . ^^^ The nuclear localization of MEK 5 and ERK 5 is different from that of ERK1 / 2 and MEK1 / 2 in resting cells , indicating that each MAPK cascade uses distinct mechanisms to transmit extracellular signals to their nuclear targets . . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Dose response studies demonstrated a bell shaped profile of fMLP stimulated MEK 5 and ERK 5 activation , but this was left shifted when compared with the profile of fMLP stimulated chemotaxis . ^^^ Kinetics studies demonstrated increases in kinase activity within 2 min , peaking at 3 5 min , and MEK 5 activation was more persistent than that of ERK 5 . ^^^ |
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| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| OBJECTIVE : To explore the change of gene expression of extracellular signal regulated protein kinase 5 ( ERK 5 ) and its upstream signaling molecule ( MEK 5 ) in fetal skin of differentially developmental stages and hypertrophic scars . ^^^ METHODS : After morphological characteristics of skin of different developmental stages and hypertrophic scars were detected with pathological methods , gene expression of ERK 5 and MEK 5 was examined with reverse transcription polymerase chain reaction analysis ( RT PCR ) . ^^^ RESULTS : In early gestational fetal skin , genes of ERK 5 and MEK 5 were strongly expressed , while in late gestational skin and children skin , the expression of ERK 5 and MEK 5 was apparently decreased ( P < 0 . 05 ) . ^^^ The increase of gene transcription of ERK 5 and MEK 5 in younger fetal skin might be a reason for rapid proliferation of the skin cells and scraless healing of skin . ^^^ The activation of ERK 5 gene expression in hypertrophic scars versus normal skin might be one of the mechanisms controlling the formation of hypertrophic scars , in which the role of MEK 5 needed to be further studied . . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| The increase in BEC proliferation was accompanied by overexpression of MAPK / extracellular signal regulated protein kinase ( ERK ) kinase 5 ( MEK 5 ) , and subsequent phosphorylation of ERK 5 in vitro . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| ERK 5 activation was blocked by the MEK 5 inhibitor U 0126 and expression of a dominant negative MEK 5 mutant . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| They further show that the activating phosphorylation of ERK 5 by MEK 5 results in the dissociation of the binding between the N and C terminal halves and thus inhibits nuclear export of ERK 5 , causing its nuclear import . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| We showed previously that p 90 RSK was activated in cells expressing an activated mutant of MEK 5 , the activator of the MAP kinase ERK 5 . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Lentiviral gene delivery of a dominant negative ERK 5 or dominant negative MAP kinase kinase 5 reduced the number of neurons generated from rat cortical progenitor cells in culture , whereas constitutive activation of ERK 5 increased the production of neurons . ^^^ |
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| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Here , we describe a constitutively active form of the MAP kinase kinase , MEK 5 ( D ) , which selectively activates BMK 1 but not other MAP kinases in vivo . ^^^ Through utilization of MEK 5 ( D ) , we have determined that a member of the MEF 2 transcription factor family , MEF2C , is a protein substrate of BMK 1 . ^^^ |
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| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| In contrast to Erk1 / 2 , EGF mediated activation of Bmk 1 occurs independently of Ras and requires the MAP kinase kinase Mek 5 . ^^^ |
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| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Only those cells expressing MAP / ERK kinase 5 ( MEK 5 ) plus ERK 5 or MEF 2 constructs underwent apoptosis , indicating that overexpression of either is sufficient to induce medulloblastoma cell death . ^^^ Expression of a dominant negative MEF 2 or small interfering RNA for the ERK 5 activator , MEK 5 , significantly inhibited neurotrophin 3 induced cell death . ^^^ |
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| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Expression of erk 5 short hairpin or a dominant negative form of the ERK 5 upstream activator , MEK 5 , in T cells led to downregulation of LKLF , increased cell size and upregulation of activation markers . ^^^ |
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| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Selective activation of the ERK 5 cascade by transfecting constitutively active MEK 5 and wildtype ERK 5 induced a reporter gene driven by the IL 2 promoter while barely affecting CD 69 expression . ^^^ |
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| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Recently , the targeted deletions of the erk 5 and the mek 5 genes in mice have provided genetic evidence that the ERK 5 cascade is a non redundant signalling pathway essential for normal cardiovascular development . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| MEKK 3 directly regulates MEK 5 activity as part of the big mitogen activated protein kinase 1 ( BMK 1 ) signaling pathway . ^^^ Previous studies have identified MEK 5 as a cellular kinase directly regulating BMK 1 activity ; however , signaling molecules that directly regulate MEK 5 activity have not yet been defined . ^^^ In addition , we show that a dominant active form of MEKK 3 stimulates BMK 1 activity through MEK 5 . ^^^ Taken together , these results identify MEKK 3 as a kinase that regulates the activity of MEK 5 and BMK 1 during growth factor induced cellular stimulation . . ^^^ |
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| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| By yeast two hybrid library screening , we have identified MEK 5 , the MAPK kinase in the big mitogen activated protein kinase 1 ( BMK 1 ) / ERK5 pathway , as a binding partner for MEKK 2 . ^^^ |
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| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| BMK 1 activation by H ( 2 ) O ( 2 ) was inhibited by both PD 98059 and U 0126 , which were reported to inhibit MEK 5 as well as MEK1 / 2 . c Src was suggested to be involved in BMK 1 activation from the experiments with herbimycin A and PP 2 , specific inhibitors of Src family kinases . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Transfection studies with dominant negative constructs of the protein kinase MEK 1 and MEK 5 suggested an important role for BMK 1 in flow mediated regulation of TNF signals . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Here , we report that inhibition of BMK 1 by a dominant negative form of MEK 5 or pharmacologic inhibition of p 38 by SB 203580 additively suppress serum induced VSMC proliferation . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Transfection studies with dominant negative constructs of the protein kinase MEK 5 suggested an important role for big mitogen activated protein kinase 1 ( BMK 1 ) in flow mediated regulation of EC activation by TNF alpha . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| To activate BMK 1 , we overexpressed constitutively active ( CA ) MEK 5 in bovine lung microvascular ECs ( BLMECs ) . ^^^ Analysis of cell viability with MTT assay showed that activation of BMK 1 by CA MEK 5 significantly improved cell viability from 48 % to 87 % and decreased apoptotic cells from 49 % to 10 % . ^^^ Analysis of antiapoptotic mechanisms showed that both shear stress and CA MEK 5 stimulated phosphorylation of Bad on Ser 112 and Ser 136 , whereas DN BMK 1 inhibited phosphorylation . ^^^ |
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| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Finally , transfection of dominant negative MEK 5 , which is an upstream regulator of BMK 1 , abolished the BMK 1 mediated rat mesangial cell proliferation stimulated by high glucose . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Of the two isoforms upstream of MAPK kinase 5 ( MEK 5 ) known to exist , only the longer MEK5alpha isoform potently activates BMK 1 . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| BMK 1 activation by constitutively active ( CA ) MEK 5 inhibited HIF1alpha activity by 46+ / 4 % , suggesting BMK 1 functions as a negative regulator of HIF1alpha activation . ^^^ The negative effect of BMK 1 on HIF1alpha was functionally important because transfection with CA MEK 5 significantly decreased EC migration by 68+ / 10 % , and inhibited angiogenesis ( in vitro Matrigel assay ) by 76+ / 7 % . ^^^ |
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| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Transfection of dominant negative MAP kinase / ERK kinase 5 ( MEK 5 ) , which is an upstream regulator of BMK 1 , partially inhibited aldosterone induced RASMC proliferation , which was almost completely inhibited by MEK inhibitor PD 98059 . ^^^ |
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| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| Here , we show that MEK 5 and big MAP kinase 1 ( BMK 1 ) function downstream of MEKK 3 in a signaling cascade that induces calcineurin activity through phosphorylation of MCIP 1 . ^^^ |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13164 and Q13163 |
Pubmed |
SVM Score :0.0 |
| NA |
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