« Previous Abstract"Effect of inoculum type, packing material and operational conditions on the biofiltration of a mixture of hydrophobic volatile organic compounds in air"    Next AbstractDual role for membrane localization in yeast MAP kinase cascade activation and its contribution to signaling fidelity »

Mol Cell Biol

Title:		Cdc42 regulation of kinase activity and signaling by the yeast p21-activated kinase Ste20
Author(s):		Lamson RE; Winters MJ; Pryciak PM;
Address:		"Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA"
Journal Title:		Mol Cell Biol
Year:		2002
Volume:		22
Issue:		9
Page Number:		2939 - 2951
DOI:		10.1128/MCB.22.9.2939-2951.2002
ISSN/ISBN:		0270-7306 (Print) 1098-5549 (Electronic) 0270-7306 (Linking)
Abstract:		"The Saccharomyces cerevisiae kinase Ste20 is a member of the p21-activated kinase (PAK) family with several functions, including pheromone-responsive signal transduction. While PAKs are usually activated by small G proteins and Ste20 binds Cdc42, the role of Cdc42-Ste20 binding has been controversial, largely because Ste20 lacking its entire Cdc42-binding (CRIB) domain retains kinase activity and pheromone response. Here we show that, unlike CRIB deletion, point mutations in the Ste20 CRIB domain that disrupt Cdc42 binding also disrupt pheromone signaling. We also found that Ste20 kinase activity is stimulated by GTP-bound Cdc42 in vivo and this effect is blocked by the CRIB point mutations. Moreover, the Ste20 CRIB and kinase domains bind each other, and mutations that disrupt this interaction cause hyperactive kinase activity and bypass the requirement for Cdc42 binding. These observations demonstrate that the Ste20 CRIB domain is autoinhibitory and that this negative effect is antagonized by Cdc42 to promote Ste20 kinase activity and signaling. Parallel results were observed for filamentation pathway signaling, suggesting that the requirement for Cdc42-Ste20 interaction is not qualitatively different between the mating and filamentation pathways. While necessary for pheromone signaling, the role of the Cdc42-Ste20 interaction does not require regulation by pheromone or the pheromone-activated G beta gamma complex, because the CRIB point mutations also disrupt signaling by activated forms of the kinase cascade scaffold protein Ste5. In total, our observations indicate that Cdc42 converts Ste20 to an active form, while pathway stimuli regulate the ability of this active Ste20 to trigger signaling through a particular pathway"
Keywords:		"Amino Acid Sequence Intracellular Signaling Peptides and Proteins MAP Kinase Kinase Kinases Molecular Sequence Data Pheromones/pharmacology Point Mutation Protein Binding Protein Serine-Threonine Kinases/chemistry/genetics/*metabolism Protein Structure, T;"
Notes:		"MedlineLamson, Rachel E Winters, Matthew J Pryciak, Peter M eng R01 GM057769-04/GM/NIGMS NIH HHS/ R01 GM057769/GM/NIGMS NIH HHS/ GM57769/GM/NIGMS NIH HHS/ R01 GM057769-05/GM/NIGMS NIH HHS/ R01 GM057769-03/GM/NIGMS NIH HHS/ Research Support, U.S. Gov't, P.H.S. 2002/04/10 Mol Cell Biol. 2002 May; 22(9):2939-51. doi: 10.1128/MCB.22.9.2939-2951.2002"