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Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1

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Abstract

In higher eukaryotes, the Ras and Raf-1 proto-oncoproteins transduce growth and differentiation signals initiated by tyrosine kinases. The Ras polypeptide and the amino-terminal regulatory domain of Raf-1(residues 1–257) are shown to interact, directly in vitro and in a yeast expression system. Raf-1(1-257) binds GTP-Ras in preference to GDP-Ras, and inhibits Ras-GAP activity. Mutations in and around the Ras effector domain impair Ras binding to Raf-1(1-257) and Ras transforming activity in parallel.

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Authors and Affiliations

  1. The Diabetes Unit and Medical Services,

    Xian-Feng Zhang, Jeffrey Settleman, John Kyriakis, Erika Takeuchi-Suzuki, Stephen J. Elledge, Mark S. Marshall, Joseph T. Bruder, Ulf R. Rapp & Joseph Avruch

  2. the Department of Medicine, Harvard Medical School,

    Xian-Feng Zhang, Jeffrey Settleman, John Kyriakis, Erika Takeuchi-Suzuki, Stephen J. Elledge, Mark S. Marshall, Joseph T. Bruder, Ulf R. Rapp & Joseph Avruch

  3. The Cancer Center, Massachusetts General Hospital East, 149 13th Street, Charlestown, Massachusetts, 02129, USA

    Jeffrey Settleman

  4. Department of Biochemistry, Baylor College of Medicine, 1 Baylor Plaza, Houston, Texas, 77030, USA

    Stephen J. Elledge

  5. Laboratory of Viral Carcinogenesis, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland, 21702, USA

    Joseph T. Bruder & Ulf R. Rapp

  6. Department of Medicine, Hematology-Oncology Section and Walther Oncology Center, Indiana University School of Medicine, Indianapolis, Indiana, 46202, USA

    Mark S. Marshall

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  1. Xian-Feng Zhang
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  9. Joseph Avruch
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Zhang, XF., Settleman, J., Kyriakis, J. et al. Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1. Nature 364, 308–313 (1993). https://doi.org/10.1038/364308a0

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