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J Biol Chem

Title:		Identification of novel pheromone-response regulators through systematic overexpression of 120 protein kinases in yeast
Author(s):		Burchett SA; Scott A; Errede B; Dohlman HG;
Address:		"Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06536, USA"
Journal Title:		J Biol Chem
Year:		2001
Volume:		20010503
Issue:		28
Page Number:		26472 - 26478
DOI:		10.1074/jbc.M103436200
ISSN/ISBN:		0021-9258 (Print) 0021-9258 (Linking)
Abstract:		"Protein kinases are well known to transmit and regulate signaling pathways. To identify additional regulators of the pheromone signaling apparatus in yeast, we evaluated an array of 120 likely protein kinases encoded by the yeast genome. Each kinase was fused to glutathione S-transferase, overexpressed, and tested for changes in pheromone responsiveness in vivo. As expected, several known components of the pathway (YCK1, STE7, STE11, FUS3, and KSS1) impaired the growth arrest response. Seven other kinases also interfered with pheromone-induced growth arrest; in rank order they are as follows: YKL116c (renamed PRR1) = YDL214c (renamed PRR2) > YJL141c (YAK1, SRA1) > YNR047w = YCR091w (KIN82) = YIL095w (PRK1) > YCL024w (KCC4). Inhibition of pheromone signaling by PRR1, but not PRR2, required the glutathione S-transferase moiety. Both kinases inhibited gene transcription after stimulation with pheromone, a constitutively active kinase mutant STE11-4, or overexpression of the transcription factor STE12. Neither protein altered the ability of the mitogen-activated protein kinase (MAPK) Fus3 to feedback phosphorylate a known substrate, the MAPK kinase Ste7. These results reveal two new components of the pheromone-signaling cascade in yeast, each acting at a point downstream of the MAPK"
Keywords:		"Amino Acid Sequence *Fungal Proteins/biosynthesis/genetics *Gene Expression Regulation, Fungal Molecular Sequence Data Pheromones/metabolism Protein Kinases/biosynthesis/*genetics Saccharomyces cerevisiae Sequence Alignment;"
Notes:		"MedlineBurchett, S A Scott, A Errede, B Dohlman, H G eng R01 GM055316/GM/NIGMS NIH HHS/ R01 GM059167/GM/NIGMS NIH HHS/ GM39852/GM/NIGMS NIH HHS/ GM59167/GM/NIGMS NIH HHS/ GM55316/GM/NIGMS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2001/05/05 J Biol Chem. 2001 Jul 13; 276(28):26472-8. doi: 10.1074/jbc.M103436200. Epub 2001 May 3"