Abstract
A new brain serine/threonine protein kinase may be a target for the p21ras-related proteins Cdc42 and Rac1. The kinase sequence is related to that of the yeast protein STE20, implicated in pheromone-response pathways. The kinase complexes specifically with activated (GTP-bound) p21, inhibiting p21 GTPase activity and leading to kinase autophosphorylation and activation. Autophosphorylated kinase has a decreased affinity for Cdc42/Rac, freeing the p21 for further stimulatory activities or downregulation by GTPase-activating proteins. This bimolecular interaction provides a model for studying p21 regulation of mammalian phosphorylation signalling pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Brain / enzymology*
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Cattle
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Enzyme Activation
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GTP Phosphohydrolases / antagonists & inhibitors
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GTP-Binding Proteins / metabolism*
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Guanosine Diphosphate / metabolism
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Guanosine Triphosphate / metabolism
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Intracellular Signaling Peptides and Proteins
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MAP Kinase Kinase Kinases
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Molecular Sequence Data
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Phosphorylation
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Protein Binding
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Protein Serine-Threonine Kinases / metabolism*
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Protein-Tyrosine Kinases / metabolism
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Rats
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Saccharomyces cerevisiae Proteins*
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Sequence Homology, Amino Acid
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Signal Transduction
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p21-Activated Kinases
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rac GTP-Binding Proteins
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rho GTP-Binding Proteins
Substances
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Intracellular Signaling Peptides and Proteins
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Saccharomyces cerevisiae Proteins
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Guanosine Diphosphate
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Guanosine Triphosphate
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Protein-Tyrosine Kinases
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Protein Serine-Threonine Kinases
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p21-Activated Kinases
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MAP Kinase Kinase Kinases
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STE20 protein, S cerevisiae
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GTP Phosphohydrolases
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GTP-Binding Proteins
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rac GTP-Binding Proteins
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rho GTP-Binding Proteins