Multiple regulatory domains on the Byr2 protein kinase

Tu, H., Barr, M., Dong, D. L., Wigler, M. H. (October 1997) Multiple regulatory domains on the Byr2 protein kinase. Mol Cell Biol, 17 (10). pp. 5876-87. ISSN 0270-7306 (Print)

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Abstract

Byr2 protein kinase, a homolog of mammalian mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEKK) and Saccharomyces cerevisiae STE11, is required for pheromone-induced sexual differentiation in the fission yeast Schizosaccharomyces pombe. Byr2 functions downstream of Ste4, Ras1, and the membrane-associated receptor-coupled heterotrimeric G-protein alpha subunit, Gpa1. Byr2 has a distinctive N-terminal kinase regulatory domain and a characteristic C-terminal kinase catalytic domain. Ste4 and Ras1 interact with the regulatory domain of Byr2 directly. Here, we define the domains of Byr2 that bind Ste4 and Ras1 and show that the Byr2 regulatory domain binds to the catalytic domain in the two-hybrid system. Using Byr2 mutants, we demonstrate that these direct physical interactions are all required for proper signaling. In particular, the physical association between Byr2 regulatory and catalytic domains appears to result in autoinhibition, the loss of which results in kinase activation. Furthermore, we provide evidence that Shk1, the S. pombe homolog of the STE20 protein kinase, can directly antagonize the Byr2 intramolecular interaction, possibly by phosphorylating Byr2.

Item Type:	Paper
Uncontrolled Keywords:	Cloning, Molecular Fungal Proteins genetics metabolism GTP-Binding Protein beta Subunits GTP-Binding Proteins metabolism Genes Fungal genetics Heterotrimeric GTP Binding Proteins MAP Kinase Kinase Kinases Point Mutation Protein Binding Protein Kinases genetics metabolism Protein-Serine-Threonine Kinases metabolism Recombinant Fusion Proteins Saccharomyces cerevisiae genetics Saccharomyces cerevisiae Proteins Schizosaccharomyces enzymology genetics physiology Schizosaccharomyces pombe Proteins Spores, Fungal ras Proteins metabolism
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 > DNA, RNA structure, function, modification > genes, structure and function > gene regulation bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > gene regulation 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:	Wigler, Michael H.
Communities:	CSHL labs > Wigler lab
Depositing User:	CSHL Librarian
Date:	October 1997
Date Deposited:	06 Apr 2012 14:09
Last Modified:	04 Nov 2016 20:26
PMCID:	PMC232435
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/25993

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