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Science 2 January 1998:
Vol. 279. no. 5347, pp. 88 - 91
DOI: 10.1126/science.279.5347.88
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Reports

Dimerization-Induced Inhibition of Receptor Protein Tyrosine Phosphatase Function Through an Inhibitory Wedge

Ravindra Majeti, Alexandrine M. Bilwes, Joseph P. Noel, Tony Hunter, Arthur Weiss *

The function and regulation of the receptorlike transmembrane protein tyrosine phosphatases (RPTPs) are not well understood. Ligand-induced dimerization inhibited the function of the epidermal growth factor receptor (EGFR)-RPTP CD45 chimera (EGFR-CD45) in T cell signal transduction. Properties of mutated EGFR-CD45 chimeras supported a general model for the regulation of RPTPs, derived from the crystal structure of the RPTPalpha membrane-proximal phosphatase domain. The phosphatase domain apparently forms a symmetrical dimer in which the catalytic site of one molecule is blocked by specific contacts with a wedge from the other.

R. Majeti and A. Weiss, Biomedical Sciences Graduate Program, Departments of Microbiology and Immunology and of Medicine and the Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA.
A. M. Bilwes and J. P. Noel, Structural Biology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
T. Hunter, Molecular Biology and Virology Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
*   To whom correspondence should be addressed. E-mail: aweiss{at}itsa.ucsf.edu

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