TY - JOUR
T1 - 14-3-3 proteins are required for maintenance of Raf-1 phosphorylation and kinase activity
AU - Thorson, John A.
AU - Yu, Lily W.K.
AU - Hsu, Alice L.
AU - Shih, Neng Yao
AU - Graves, Paul R.
AU - William Tanner, J.
AU - Allen, Paul M.
AU - Piwnica-Worms, Helen
AU - Shaw, Andrey S.
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
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U2 - 10.1128/MCB.18.9.5229
DO - 10.1128/MCB.18.9.5229
M3 - Article
C2 - 9710607
AN - SCOPUS:0031841424
SN - 0270-7306
VL - 18
SP - 5229
EP - 5238
JO - Molecular and cellular biology
JF - Molecular and cellular biology
IS - 9
ER -