title: Krh1p and Krh2p act downstream of the Gpa2p G(alpha) subunit to negatively regulate haploid invasive growth.
abstract: The yeast G(alpha) subunit Gpa2p and its coupled receptor Gpr1p function in a signaling pathway that is required for the transition to pseudohyphal and invasive growth. A two-hybrid screen using a constitutively active allele of GPA2 identified the KRH1 gene as encoding a potential binding partner of Gpa2p. Strains containing deletions of KRH1 and its homolog KRH2 were hyper-invasive and displayed a high level of expression of FLO11, a gene involved in pseudohyphal and invasive growth. Therefore, KRH1 and KRH2 encode negative regulators of the invasive growth pathway. Cells containing krh1Delta krh2Delta mutations also displayed increased sensitivity to heat shock and decreased sporulation efficiency, indicating that Krh1p and Krh2p regulate multiple processes controlled by the cAMP/PKA pathway. The krh1Delta krh2Delta mutations suppressed the effect of a gpa2Delta mutation on FLO11 expression and eliminated the effect of a constitutively active GPA2 allele on induction of FLO11 and heat shock sensitivity, suggesting that Krh1p and Krh2p act downstream of Gpa2p. The Sch9p kinase was not required for the signal generated by deletion of KRH1 and KRH2; however, the cAMP-dependent kinase Tpk2p was required for generation of this signal. These results support a model in which activation of Gpa2p relieves the inhibition exerted by Krh1p and Krh2p on components of the cAMP/PKA signaling pathway.
authors.affiliation: Brookdale Department of Molecular, Cell, and Developmental Biology, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Batlle
authors.forename: Ailan
authors.initials: A
authors.lastname: Lu
authors.forename: David A
authors.initials: DA
authors.lastname: Green
authors.forename: Yong
authors.initials: Y
authors.lastname: Xue
authors.forename: Jeanne P
authors.initials: JP
authors.lastname: Hirsch
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D002455:Cell Division / Q000502:physiology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D015536:Down-Regulation / Q000235:genetics*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D044385:GTP-Binding Protein alpha Subunits; D015966:Gene Expression Regulation, Fungal / Q000235:genetics; D006238:Haploidy; D018869:Heat-Shock Response / Q000235:genetics; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018076:DNA, Complementary; C110690:FLO11 protein, S cerevisiae; D005656:Fungal Proteins; C476991:GPB1 protein, S cerevisiae; D044385:GTP-Binding Protein alpha Subunits; C476990:Gpb2 protein, S cerevisiae; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; D000242:Cyclic AMP; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; C457179:TPK2 protein, S cerevisiae; C083907:Gpa2 protein, S cerevisiae; D020962:Heterotrimeric GTP-Binding Proteins