Phosphatidylinositol 3-kinase regulates Raf1 through Pak phosphorylation of serine 338

A. Chaudhary, W. G. King, M. D. Mattaliano, J. A. Frost, B. Diaz, D. K. Morrison, M. H. Cobb, M. S. Marshall, J. S. Brugge

Research output: Contribution to journalArticle

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Abstract

We have previously shown that inhibition of phosphatidylinositol (PI)3-kinase severely attenuates the activation of extracellular signal-regulated kinase (Erk) following engagement of integrin/fibronectin receptors and that Raf is the critical target of PI 3-kinase regulation [1]. To investigate how PI 3-kinase regulates Raf, we examined sites on Raf1 required for regulation by PI 3-kinase and explored the mechanisms involved in this regulation. Serine 338 (Ser338), which was critical for fibronectin stimulation of Raf1, was phosphorylated in a PI 3-kinase-dependent manner following engagement of fibronectin receptors. In addition, fibronectin activation of a Raf1 mutant containing a phospho-mimic mutation (S338D) was independent of PI 3-kinase. Furthermore, integrin-induced activation of the serine/threonine kinase Pak-1, which has been shown to phosphorylate Raf1 Ser338, was also dependent on PI 3-kinase activity and expression of a kinase-inactive Pak-1 mutant blocked phosphorylation of Raf1 Ser338. These results indicate that PI 3-kinase regulates phosphorylation of Raf1 Ser338 through the serine/threonine kinase Pak. Thus, phosphorylation of Raf1 Ser338 through PI 3-kinase and Pak provides a co-stimulatory signal which together with Ras leads to strong activation of Raf1 kinase activity by integrins.

Original languageEnglish (US)
Pages (from-to)551-554
Number of pages4
JournalCurrent Biology
Volume10
Issue number9
DOIs
StatePublished - May 1 2000

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Phosphatidylinositol 3-Kinase
Phosphorylation
phosphatidylinositol 3-kinase
serine
Serine
phosphorylation
fibronectins
integrins
phosphotransferases (kinases)
Fibronectin Receptors
Chemical activation
Integrins
Protein-Serine-Threonine Kinases
Fibronectins
threonine
Phosphotransferases
mutants
receptors
Extracellular Signal-Regulated MAP Kinases
mitogen-activated protein kinase

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Chaudhary, A., King, W. G., Mattaliano, M. D., Frost, J. A., Diaz, B., Morrison, D. K., ... Brugge, J. S. (2000). Phosphatidylinositol 3-kinase regulates Raf1 through Pak phosphorylation of serine 338. Current Biology, 10(9), 551-554. https://doi.org/10.1016/S0960-9822(00)00475-9

Phosphatidylinositol 3-kinase regulates Raf1 through Pak phosphorylation of serine 338. / Chaudhary, A.; King, W. G.; Mattaliano, M. D.; Frost, J. A.; Diaz, B.; Morrison, D. K.; Cobb, M. H.; Marshall, M. S.; Brugge, J. S.

In: Current Biology, Vol. 10, No. 9, 01.05.2000, p. 551-554.

Research output: Contribution to journalArticle

Chaudhary, A, King, WG, Mattaliano, MD, Frost, JA, Diaz, B, Morrison, DK, Cobb, MH, Marshall, MS & Brugge, JS 2000, 'Phosphatidylinositol 3-kinase regulates Raf1 through Pak phosphorylation of serine 338', Current Biology, vol. 10, no. 9, pp. 551-554. https://doi.org/10.1016/S0960-9822(00)00475-9
Chaudhary A, King WG, Mattaliano MD, Frost JA, Diaz B, Morrison DK et al. Phosphatidylinositol 3-kinase regulates Raf1 through Pak phosphorylation of serine 338. Current Biology. 2000 May 1;10(9):551-554. https://doi.org/10.1016/S0960-9822(00)00475-9
Chaudhary, A. ; King, W. G. ; Mattaliano, M. D. ; Frost, J. A. ; Diaz, B. ; Morrison, D. K. ; Cobb, M. H. ; Marshall, M. S. ; Brugge, J. S. / Phosphatidylinositol 3-kinase regulates Raf1 through Pak phosphorylation of serine 338. In: Current Biology. 2000 ; Vol. 10, No. 9. pp. 551-554.
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