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Abstract

To identify proteins that may participate in the activation of the protein kinase Raf, proteins that interact with Raf were selected in a two-hybrid screen. Two members of the 14-3-3 protein family were isolated that interacted with both the amino terminal regulatory regions of Raf and the kinase domain of Raf, but did not compete with the guanine nucleotide-binding protein Ras for binding to Raf. 14-3-3 proteins associated with Raf in mammalian cells and accompanied Raf to the membrane in the presence of activated Ras. In yeast cells expressing Raf and MEK, mammalian 14-3-3 ζ or 14-3-3 ζ activated Raf to a similar extent as did expression of Ras. Therefore, 14-3-3 proteins may participate in or be required for the regulation of Raf function. These findings suggest a role for 14-3-3 proteins in Raf-mediated signal transduction.

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Science
Volume 265 | Issue 5179
16 September 1994

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Published in print: 16 September 1994

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Ellen Freed
Onyx Pharmaceuticals, Richmond, CA 94806-5206, USA.
Marc Symons
Onyx Pharmaceuticals, Richmond, CA 94806-5206, USA.
Susan G. Macdonald
Onyx Pharmaceuticals, Richmond, CA 94806-5206, USA.
Frank McCormick
Onyx Pharmaceuticals, Richmond, CA 94806-5206, USA.
Rosamaria Ruggieri
Onyx Pharmaceuticals, Richmond, CA 94806-5206, USA.

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