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Mol Cell

Title:		Regulation of cell signaling dynamics by the protein kinase-scaffold Ste5
Author(s):		Hao N; Nayak S; Behar M; Shanks RH; Nagiec MJ; Errede B; Hasty J; Elston TC; Dohlman HG;
Address:		"Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA"
Journal Title:		Mol Cell
Year:		2008
Volume:		30
Issue:		5
Page Number:		649 - 656
DOI:		10.1016/j.molcel.2008.04.016
ISSN/ISBN:		1097-4164 (Electronic) 1097-2765 (Print) 1097-2765 (Linking)
Abstract:		"Cell differentiation requires the ability to detect and respond appropriately to a variety of extracellular signals. Here we investigate a differentiation switch induced by changes in the concentration of a single stimulus. Yeast cells exposed to high doses of mating pheromone undergo cell division arrest. Cells at intermediate doses become elongated and divide in the direction of a pheromone gradient (chemotropic growth). Either of the pheromone-responsive MAP kinases, Fus3 and Kss1, promotes cell elongation, but only Fus3 promotes chemotropic growth. Whereas Kss1 is activated rapidly and with a graded dose-response profile, Fus3 is activated slowly and exhibits a steeper dose-response relationship (ultrasensitivity). Fus3 activity requires the scaffold protein Ste5; when binding to Ste5 is abrogated, Fus3 behaves like Kss1, and the cells no longer respond to a gradient or mate efficiently with distant partners. We propose that scaffold proteins serve to modulate the temporal and dose-response behavior of the MAP kinase"
Keywords:		"Adaptor Proteins, Signal Transducing/*metabolism Cell Differentiation/drug effects Enzyme Activation *MAP Kinase Signaling System Mitogen-Activated Protein Kinases/*metabolism Pheromones/pharmacology Saccharomyces cerevisiae/*cytology/drug effects/*enzymo;"
Notes:		"MedlineHao, Nan Nayak, Sujata Behar, Marcelo Shanks, Ryan H Nagiec, Michal J Errede, Beverly Hasty, Jeffrey Elston, Timothy C Dohlman, Henrik G eng R01 GM073180-02/GM/NIGMS NIH HHS/ R01 GM073180-04/GM/NIGMS NIH HHS/ R01 GM073180/GM/NIGMS NIH HHS/ R01 GM073180-03/GM/NIGMS NIH HHS/ R01 GM073180-01/GM/NIGMS NIH HHS/ T32 HL007089/HL/NHLBI NIH HHS/ 2008/06/10 Mol Cell. 2008 Jun 6; 30(5):649-56. doi: 10.1016/j.molcel.2008.04.016"