Neutralizing Monoclonal Antibody Against Ras Oncogene Product p21 Which Impairs Guanine Nucleotide Exchange

Seisuke Hattori1 Department of Pure and Applied Sciences, University of Tokyo, Komaba, Meguro-ku, Tokyo153, Japan

David J. Clanton2 Laboratory of Molecular Oncology, National Cancer Institute, Frederick, Maryland21701

Takaya Satoh3 Department of Chemistry, Institute of Medical Science, University of Tokyo, Tokyo108, Japan

Shun Nakamura3 Department of Chemistry, Institute of Medical Science, University of Tokyo, Tokyo108, Japan

Yoshito Kaziro2 Laboratory of Molecular Oncology, National Cancer Institute, Frederick, Maryland21701

Masao Kawakita1 Department of Pure and Applied Sciences, University of Tokyo, Komaba, Meguro-ku, Tokyo153, Japan

Thomas Y. Shih2 Laboratory of Molecular Oncology, National Cancer Institute, Frederick, Maryland21701

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Abstract

The neutralizing monoclonal antibody Y13-259 severely hampers the nucleotide exchange reaction between p21-bound and exogenous guanine nucleotides but does not interfere with the association of GDP to p21. These results suggest that the nucleotide exchange reaction is critical for p21 function. Interestingly, the v-ras p21 has a much faster dissociation rate than the p21 of the c-ras proto-oncogene.

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Neutralizing Monoclonal Antibody Against Ras Oncogene Product p21 Which Impairs Guanine Nucleotide Exchange

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Neutralizing Monoclonal Antibody Against Ras Oncogene Product p21 Which Impairs Guanine Nucleotide Exchange

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