Genetic evidence for Pak1 autoinhibition and its release by Cdc42

Tu, H., Wigler, M. H. (January 1999) Genetic evidence for Pak1 autoinhibition and its release by Cdc42. Mol Cell Biol, 19 (1). pp. 602-11. ISSN 0270-7306 (Print)

[img]
Preview
PDF (Paper)
Genetic evidence for Pak1 autoinhibition and its release by Cdc42.pdf - Published Version

Download (2203Kb) | Preview
URL: https://www.ncbi.nlm.nih.gov/pubmed/9858584
DOI: 10.1128/MCB.19.1.602

Abstract

Pak1 protein kinase of Schizosaccharomyces pombe, a member of the p21-GTPase-activated protein kinase (PAK) family, participates in signaling pathways including sexual differentiation and morphogenesis. The regulatory domain of PAK proteins is thought to inhibit the kinase catalytic domain, as truncation of this region renders kinases more active. Here we report the detection in the two-hybrid system of the interaction between Pak1 regulatory domain and the kinase catalytic domain. Pak1 catalytic domain binds to the same highly conserved region on the regulatory domain that binds Cdc42, a GTPase protein capable of activating Pak1. Two-hybrid, mutant, and genetic analyses indicated that this intramolecular interaction rendered the kinase in a closed and inactive configuration. We show that Cdc42 can induce an open configuration of Pak1. We propose that Cdc42 interaction disrupts the intramolecular interactions of Pak1, thereby releasing the kinase from autoinhibition.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Animals Binding Sites Catalysis Cell Cycle Proteins genetics metabolism Conserved Sequence Enzyme Activation GTP Binding Proteins genetics metabolism Molecular Sequence Data Mutagenesis Protein Conformation Protein Serine Threonine Kinases antagonists & inhibitors chemistry genetics metabolism Saccharomyces cerevisiae Proteins Schizosaccharomyces enzymology genetics Sequence Homology Amino Acid cdc42 GTP-Binding Protein Saccharomyces cerevisiae
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene expression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein characterization
CSHL Authors:
Communities: CSHL labs > Wigler lab
Depositing User: CSHL Librarian
Date: January 1999
Date Deposited: 06 Apr 2012 14:02
Last Modified: 04 Nov 2016 20:27
PMCID: PMC83918
Related URLs:
URI: http://repository.cshl.edu/id/eprint/25992

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving