Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control

Jessie M. English, Gray Pearson, Tish Hockenberry, Latha Shivakumar, Michael A. White, Melanie H. Cobb

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

The activity of the catalytic domain of the orphan MAP kinase ERK5 is increased by Ras but not Raf-1 in cells, which suggests that ERK5 might mediate Raf-independent signaling by Ras. We found that Raf-1 does contribute to Ras activation of ERK5 but in a manner that does not correlate with Raf-1 catalytic activity. A clue to the mechanism of action of Raf-1 on ERK5 comes from the observation that endogenous Raf-1 binds to endogenous ERK5, suggesting the involvement of regulatory protein-protein interactions. This interaction is specific because Raf-1 binds only to ERK5 and not ERK2 or SAPK. Finally, we demonstrate the ERK5/MEK5 pathway is required for Raf- dependent cellular transformation and that a constitutively active form of MEK5, MEK5DD, synergizes with Raf to transform NIH 3T3 cells. These observations suggest that ERK5 plays a large role in Raf-1-mediated signal transduction.

Original languageEnglish (US)
Pages (from-to)31588-31592
Number of pages5
JournalJournal of Biological Chemistry
Volume274
Issue number44
DOIs
StatePublished - Oct 29 1999

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Mitogen-Activated Protein Kinase 7
NIH 3T3 Cells
Signal transduction
Growth
Signal Transduction
Catalyst activity
Catalytic Domain
Proteins
Chemical activation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control. / English, Jessie M.; Pearson, Gray; Hockenberry, Tish; Shivakumar, Latha; White, Michael A.; Cobb, Melanie H.

In: Journal of Biological Chemistry, Vol. 274, No. 44, 29.10.1999, p. 31588-31592.

Research output: Contribution to journalArticle

English, Jessie M. ; Pearson, Gray ; Hockenberry, Tish ; Shivakumar, Latha ; White, Michael A. ; Cobb, Melanie H. / Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 44. pp. 31588-31592.
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