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 journalArticlepeer-review

107 Scopus citations


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
Issue number44
StatePublished - Oct 29 1999

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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