ERK5 and ERK2 cooperate to regulate NF-kappaB and cell transformation.
We have previously demonstrated an involvement of MEK5 and ERK5 in RafBXB-stimulated focus formation in NIH3T3 cells. We find here that MEK5 and ERK5 cooperate with the RafBXB effectors MEK1/2 and ERK1/2 to induce foci. To further understand MEK5-ERK5-dependent signaling, we examined potential MEK5-ERK5 effectors that might influence focus-forming activity. Consistent with results from our focus-formation assays, constitutively active variants of MEK5 and MEK1 synergize to activate NF-kappaB, and MEK5 and ERK5 are required for activation of NF-kappaB by RafBXB. The MEK5-ERK5 pathway is also sufficient to activate both NF-kappaB and p90 ribosomal S6 kinase. Our results support the hypothesis that NF-kappaB and p90 ribosomal S6 kinase are involved in MEK5-ERK5-dependent focus formation and may serve as integration points for ERK5 and ERK1/2 signaling.
Pearson
G
G
Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041, USA.
English
J M
JM
White
M A
MA
Cobb
M H
MH
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D004815:Epidermal Growth Factor / Q000235:genetics; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D048369:MAP Kinase Kinase 1; D048671:MAP Kinase Kinase 5; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology*; D048054:Mitogen-Activated Protein Kinase 7; D020929:Mitogen-Activated Protein Kinase Kinases / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D019908:Proto-Oncogene Proteins c-raf / Q000502:physiology; D020218:Response Elements; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D014158:Transcription, Genetic
C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D016328:NF-kappa B; D004815:Epidermal Growth Factor; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D019893:Ribosomal Protein S6 Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048054:Mitogen-Activated Protein Kinase 7; D020928:Mitogen-Activated Protein Kinases; D048369:MAP Kinase Kinase 1; D048671:MAP Kinase Kinase 5; C482127:Map2k1 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases