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MOLECULAR-CLONING OF A NEW MEMBER OF THE P21-CDC42/RAC-ACTIVATED KINASE (PAK) FAMILY

MANSER, E; CHONG, C; ZHAO, ZS; LEUNG, T; MICHAEL, G; HALL, C; LIM, L; (1995) MOLECULAR-CLONING OF A NEW MEMBER OF THE P21-CDC42/RAC-ACTIVATED KINASE (PAK) FAMILY. J BIOL CHEM , 270 (42) 25070 - 25078. Gold open access

Abstract

A number of ''target'' proteins for the Rho family of small GTP-binding proteins have now been identified, including the protein kinases ACK and p65(PAK) (Manser, E., Leung, T., Salihuddin, H., Zhao, Z.-S., and Lim, L. (1994) Nature 367, 40-46). The purified serine/threonine kinase p65(PAK) has been shown to be directly activated by GTP-Rac1 or GTP-Cdc42. Here we report the cDNA sequence encoding a new brain-enriched PAK isoform beta-PAK, which shares 79% amino acid identity with the previously described alpha-isoform. Their mRNAs are differentially expressed in the brain, with alpha-PAK mRNA being particularly abundant in motor-associated regions. In vitro translation products of the alpha- and beta-PAK cDNAs exhibited relative molecular masses of 68,000 and 65,000, respectively, by SDS-polyacrylamide analysis. A specific beta-PAK peptide sequence was obtained from rat brain-purified p65(PAK). Recombinant alpha- and beta-PAKs exhibited an increase in kinase activity mediated by GTP-p21 induced autophosphorylation. Cdc42 was a more potent activator in vitro of alpha-PAK kinase, and the fully activated enzyme is 300 times more active than the unphosphorylated form. Interestingly the down-regulation in the binding of p21s to recombinant beta-PAK and brain p65(PAK), which is observed upon kinase activation does not occur with recombinant alpha-PAK.

Type:Article
Title:MOLECULAR-CLONING OF A NEW MEMBER OF THE P21-CDC42/RAC-ACTIVATED KINASE (PAK) FAMILY
Open access status:An open access publication
Publisher version:http://www.jbc.org/content/early/recent/0
Keywords:GTP-BINDING-PROTEIN, ACTIVATING PROTEIN, HUMAN HOMOLOG, IN-VITRO, GENE, RAS, CHIMAERIN, SEQUENCE, P21RAC, G25K
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Neurology

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