The requirement of specific membrane domains for Raf-1 phosphorylation and activation

Kendall D. Carey, Robert T. Watson, Jeffrey E. Pessin, Philip J S Stork

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Activation of Raf-1 by Ras requires recruitment to the membrane as well as additional phosphorylations, including phosphorylation at serine 338 (Ser-338) and tyrosine 341 (Tyr-341). In this study we show that Tyr-341 participates in the recruitment of Raf-1 to specialized membrane domains called "rafts," which are required for Raf-1 to be phosphorylated on Ser-338. Raf-1 is also thought to be recruited to the small G protein Rap1 upon GTP loading of Rap1. However, this does not result in Raf-1 activation. We propose that this is because Raf-1 is not phosphorylated on Tyr-341 upon recruitment to Rap1. Redirecting Rap1 to Ras-containing membranes or mimicking Tyr-341 phosphorylation of Raf-1 by mutation converts Rap1 into an activator of Raf-1. In contrast to Raf-1, B-Raf is activated by Rap1. We suggest that this is because B-Raf activation is independent of tyrosine phosphorylation. Moreover, mutants that render B-Raf dependent on tyrosine phosphorylation are no longer activated by Rap1.

Original languageEnglish (US)
Pages (from-to)3185-3196
Number of pages12
JournalJournal of Biological Chemistry
Volume278
Issue number5
DOIs
StatePublished - Jan 31 2003
Externally publishedYes

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Phosphorylation
Tyrosine
Chemical activation
Membranes
Serine
Monomeric GTP-Binding Proteins
Guanosine Triphosphate
Mutation

ASJC Scopus subject areas

  • Biochemistry

Cite this

The requirement of specific membrane domains for Raf-1 phosphorylation and activation. / Carey, Kendall D.; Watson, Robert T.; Pessin, Jeffrey E.; Stork, Philip J S.

In: Journal of Biological Chemistry, Vol. 278, No. 5, 31.01.2003, p. 3185-3196.

Research output: Contribution to journalArticle

Carey, Kendall D. ; Watson, Robert T. ; Pessin, Jeffrey E. ; Stork, Philip J S. / The requirement of specific membrane domains for Raf-1 phosphorylation and activation. In: Journal of Biological Chemistry. 2003 ; Vol. 278, No. 5. pp. 3185-3196.
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