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Genes Dev

Title:		Membrane recruitment of the kinase cascade scaffold protein Ste5 by the Gbetagamma complex underlies activation of the yeast pheromone response pathway
Author(s):		Pryciak PM; Huntress FA;
Address:		"Department of Molecular Genetics and Microbiology, University of Massachusetts Medical Center, Worcester Foundation Campus, Shrewsbury, Massachusetts 01545, USA. peter.pryciak@ummed.edu"
Journal Title:		Genes Dev
Year:		1998
Volume:		12
Issue:		17
Page Number:		2684 - 2697
DOI:		10.1101/gad.12.17.2684
ISSN/ISBN:		0890-9369 (Print) 0890-9369 (Linking)
Abstract:		"In the Saccharomyces cerevisiae pheromone response pathway, the Gbetagamma complex activates downstream responses by an unknown mechanism involving a MAP kinase cascade, the PAK-like kinase Ste20, and a Rho family GTPase, Cdc42. Here we show that Gbetagamma must remain membrane-associated after release from Galpha to activate the downstream pathway. We also show that pheromone stimulates translocation of the kinase cascade scaffold protein Ste5 to the cell surface. This recruitment requires Gbetagamma function and the Gbetagamma-binding domain of Ste5, but not the kinases downstream of Gbetagamma, suggesting that it is mediated by Gbetagamma itself. Furthermore, this event has functional significance, as artificial targeting of Ste5 to the plasma membrane, but not intracellular membranes, activates the pathway in the absence of pheromone or Gbetagamma. Remarkably, although independent of Gbetagamma, activation by membrane-targeted Ste5 requires Ste20, Cdc42, and Cdc24, indicating that their participation in this pathway does not require them to be activated by Gbetagamma. Thus, membrane recruitment of Ste5 defines a molecular activity for Gbetagamma. Moreover, our results suggest that this event promotes kinase cascade activation by delivering the Ste5-associated kinases to the cell surface kinase Ste20, whose function may depend on Cdc42 and Cdc24"
Keywords:		"*Adaptor Proteins, Signal Transducing Amino Acid Sequence *Carrier Proteins Cell Cycle Proteins/metabolism Crosses, Genetic Fungal Proteins/*metabolism GTP Phosphohydrolases/metabolism GTP-Binding Proteins/chemistry/*metabolism Genotype *Guanine Nucleotid;"
Notes:		"MedlinePryciak, P M Huntress, F A eng R01 GM057769/GM/NIGMS NIH HHS/ GM57769/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 1998/09/10 Genes Dev. 1998 Sep 1; 12(17):2684-97. doi: 10.1101/gad.12.17.2684"