Journal of Cell Science 115, e802-e802 (2002)
© 2002 The Company of Biologists Limited
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.
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]
