14-3-3 proteins are required for maintenance of Raf-1 phosphorylation and kinase activity

John A. Thorson, Lily W.K. Yu, Alice L. Hsu, Neng Yao Shih, Paul R. Graves, J. William Tanner, Paul M. Allen, Helen Piwnica-Worms, Andrey S. Shaw

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183 Scopus citations

Abstract

By binding to serine-phosphorylated proteins, 14-3-3 proteins function as effectors of serine phosphorylation. The exact mechanism of their action is, however, still largely unknown. Here we demonstrate a requirement for 14- 3-3 for Raf-1 kinase activity and phosphorylation. Expression of dominant negative forms of 14-3-3 resulted in the loss of a critical Raf-1 phosphorylation, while overexpression of 14-3-3 resulted in enhanced phosphorylation of this site. 14-3-3 levels, therefore, regulate the stoichiometry of Raf-1 phosphorylation and its potential activity in the cell. Phosphorylation of Raf-1, however, was insufficient by itself for kinase activity. Removal of 14-3-3 from phosphorylated Raf abrogated kinase activity, whereas addition of 14-3-3 restored it. This supports a paradigm in which the effects of phosphorylation on serine as well as tyrosine residues are mediated by inducible protein-protein interactions.

Original languageEnglish
Pages (from-to)5229-5238
Number of pages10
JournalMolecular and cellular biology
Volume18
Issue number9
DOIs
StatePublished - 1998

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