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J Biol Chem, Vol. 274, Issue 29, 20056-20059, July 16, 1999

COMMUNICATION
Activation of the Lck Tyrosine-protein Kinase by the Binding of the Tip Protein of Herpesvirus Saimiri in the Absence of Regulatory Tyrosine Phosphorylation

David A. Hartley, Tamara R. Hurley, James S. Hardwick, Troy C. Lund, Peter G. Medveczky, and Bartholomew M. Sefton

From the  Molecular Biology and Virology Laboratory, The Salk Institute, La Jolla, California 92037 and the  Department of Medical Microbiology, University of South Florida, Tampa, Florida 33612

The Tip protein of herpesvirus saimiri 484 binds to the Lck tyrosine-protein kinase at two sites and activates it dramatically. Lck has been shown previously to be activated by either phosphorylation of Tyr³⁹⁴ or dephosphorylation of Tyr⁵⁰⁵. We examined here whether a change in the phosphorylation of either site was required for the activation of Lck by Tip. Remarkably, mutation of both regulatory sites of tyrosine phosphorylation did not prevent activation of Lck by Tip either in vivo or in a cell free in vitro system. Tip therefore appears to be able to activate Lck through an induced conformational change that does not necessarily involve altered phosphorylation of the kinase. Tip may represent the prototype of a novel type of regulator of tyrosine-protein kinases.

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Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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