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)
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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: | https://repository.cshl.edu/id/eprint/25992 |
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