Identification and molecular cloning of a p21cdc42/rac1-activated serine/threonine kinase that is rapidly activated by thrombin in platelets.

The brain-enriched p21cdc42/rac1-activated serine/threonine kinase, p65PAK, was identified and purified on the basis of overlays with [gamma-32P]GTP-Cdc42 onto SDS-fractionated proteins (Manser, E., Leung, T., Salihuddin, H., Zhao, Z.-S., and Lim, L. (1994) Nature 367, 40-46). In this study, the ubiquitously expressed p21cdc42/rac1 binding protein with relative molecular weight of 62,000 ...
was purified from rat testes and shown to contain peptides related to PAK. It has thus been designated as the gamma-PAK isoform (alpha- and beta-isoforms being brain enriched). Isolation of gamma-PAK cDNAs show that the kinase is highly conserved with alpha-PAK in both the p2 binding and kinase domains. The purified protein exhibited kinase activity that was activated by GTP-Cdc42 or GTP-Rac1 in vitro. In platelets, a p62 in situ renaturable kinase was recognized by antibodies raised against gamma-PAK. This thrombin-activated protein kinase appears to coprecipitate with another kinase of M(r) 86,000, suggesting that PAK may be part of a thrombin-responsive signaling complex.
Mesh Terms:
Amino Acid Sequence, Animals, Base Sequence, Blood Platelets, Brain, Cell Cycle Proteins, Cloning, Molecular, DNA Primers, Enzyme Activation, GTP-Binding Proteins, Gene Expression, Humans, Male, Molecular Sequence Data, Polymerase Chain Reaction, Protein-Serine-Threonine Kinases, Rats, Recombinant Proteins, Sequence Homology, Amino Acid, Testis, Thrombin, cdc42 GTP-Binding Protein, p21-Activated Kinases
J. Biol. Chem.
Date: Nov. 03, 1995
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