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The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338

The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338 The pathway involving the signalling protein p21Ras propagates a range of extracellular signals from receptors on the cell membrane to the cytoplasm and nucleus 1 . The Ras proteins regulate many effectors, including members of the Raf family of protein kinases. Ras-dependent activation of Raf-1 at the plasma membrane involves phosphorylation events, protein–protein interactions and structural changes 2,3,4,5,6,7,8 . Phosphorylation of serine residues 338 or 339 in the catalytic domain of Raf-1 regulates its activation in response to Ras, Src and epidermal growth factor 9 , 10 . Here we show that the p21-activated protein kinase Pak3 phosphorylates Raf-1 on serine 338 in vitro and in vivo. The p21-activated protein kinases are regulated by the Rho-family GTPases Rac and Cdc42 (ref. 11). Our results indicate that signal transduction through Raf-1 depends on both Ras and the activation of the Pak pathway. As guanine-nucleotide-exchange activity on Rac can be stimulated by a Ras-dependent phosphatidylinositol-3-OH kinase 12 , 13 , a mechanism could exist through which one Ras effector pathway can be influenced by another. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Nature Springer Journals

The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338

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References (61)

Publisher
Springer Journals
Copyright
Copyright © 1998 by Macmillan Magazines Ltd.
Subject
Science, Humanities and Social Sciences, multidisciplinary; Science, Humanities and Social Sciences, multidisciplinary; Science, multidisciplinary
ISSN
0028-0836
eISSN
1476-4687
DOI
10.1038/24184
Publisher site
See Article on Publisher Site

Abstract

The pathway involving the signalling protein p21Ras propagates a range of extracellular signals from receptors on the cell membrane to the cytoplasm and nucleus 1 . The Ras proteins regulate many effectors, including members of the Raf family of protein kinases. Ras-dependent activation of Raf-1 at the plasma membrane involves phosphorylation events, protein–protein interactions and structural changes 2,3,4,5,6,7,8 . Phosphorylation of serine residues 338 or 339 in the catalytic domain of Raf-1 regulates its activation in response to Ras, Src and epidermal growth factor 9 , 10 . Here we show that the p21-activated protein kinase Pak3 phosphorylates Raf-1 on serine 338 in vitro and in vivo. The p21-activated protein kinases are regulated by the Rho-family GTPases Rac and Cdc42 (ref. 11). Our results indicate that signal transduction through Raf-1 depends on both Ras and the activation of the Pak pathway. As guanine-nucleotide-exchange activity on Rac can be stimulated by a Ras-dependent phosphatidylinositol-3-OH kinase 12 , 13 , a mechanism could exist through which one Ras effector pathway can be influenced by another.

Journal

Nature – Springer Journals

Published: Nov 12, 1998

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