QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?

New routes for Raf?

Raf1 is part of the prototypical MAP kinase cascade linking the small GTPase Ras to the MAP kinase ERK. Activation of Raf by Ras and other upstream stimuli causes it to phosphorylate MEK, which in turn phosphorylates ERK — a kinase that has numerous cytosolic and nuclear targets, including transcription factors. But are things that simple? Do Raf1 and its relatives do nothing more than link to MEK/ERK? In a Commentary on p. 1575, Alison Hindley and Walter Kolch weigh the evidence for and against ERK-independent functions of Raf kinases. Novel substrates for Raf1 have been proposed (e.g. p53 and Cdc25), but as yet none has been confirmed. Moreover, although studies in neuronal cells suggest that Raf can stimulate NF-B activity and cell differentiation independently of MEK, these experiments relied on overexpression of Raf mutants — a technique that can generate artefacts. Perhaps the strongest supporting evidence, however, is knockout work: Raf1^-/- mice exhibit normal ERK activation but increased apoptosis, which suggests that Raf1 has a MEK/ERK-independent anti-apoptotic role.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

Related articles in JCS:

Extracellular signal regulated kinase (ERK)/mitogen activated protein kinase (MAPK)-independent functions of Raf kinases

Alison Hindley and Walter Kolch
JCS 2002 115: 1575-1581. [Abstract] [Full Text]  

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?