Activation of Raf-1 by 14-3-3 proteins.
The protein Raf-1, a key mediator of mitogenesis and differentiation, associates with p21ras (refs 1-3). However, the regulation of the serine/threonine kinase activity of Raf-1 is still not understood. Using the yeast two-hybrid system, we identified two structurally related proteins that interact with the aminoterminal region of Raf-1. These proteins, 14-3-3 zeta (PLA2) and 14-3-3 beta (HS1), are members of the 14-3-3 family of proteins. Expression of 14-3-3 proteins in Xenopus oocytes enhanced Raf-1 activity and promoted Raf-1-dependent oocyte maturation. A dominant negative mutant of Raf-1 blocked the effects of 14-3-3 protein.
Fantl
W J
WJ
Daiichi Research Center, Cardiovascular Research Institute, Department of Medicine, University of California, San Francisco 94143.
Muslin
A J
AJ
Kikuchi
A
A
Martin
J A
JA
MacNicol
A M
AM
Gross
R W
RW
Williams
L T
LT
D048948:14-3-3 Proteins; D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002478:Cells, Cultured; D004789:Enzyme Activation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009865:Oocytes; D009866:Oogenesis / Q000235:genetics / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D019908:Proto-Oncogene Proteins c-raf; D011994:Recombinant Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D014446:Tyrosine 3-Monooxygenase; D014981:Xenopus
D048948:14-3-3 Proteins; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D014446:Tyrosine 3-Monooxygenase; D017346:Protein Serine-Threonine Kinases; D019908:Proto-Oncogene Proteins c-raf; D016203:CDC2 Protein Kinase