SOK2 may regulate cyclic AMP-dependent protein kinase-stimulated growth and pseudohyphal development by repressing transcription

Yeast cyclic AMP (cAMP)-dependent protein kinase (PKA) activity is essential for growth and cell cycle progression. Dependence on PKA function can be partially relieved by overexpression of a gene, SOK2, whose product has significant homology with several fungal transcription factors (StuA from Aspergillus nidulans and Phd1 from Saccharomyces cerevisiae) that are associated with cellular differentiation and development. Deletion of SOK2 is not lethal but exacerbates the growth defect of strains compromised for PKA activity. Alterations in Sok2 protein production also affect the expression of genes involved in several other PKA-regulated processes, including glycogen accumulation (GAC1) and heat shock resistance (SSA3). These results suggest SOK2 plays a general regulatory role in the PKA signal transduction pathway. Expression of the PKA catalytic subunit genes is unaltered by deletion or overexpression of SOK2. Because homozygous sok2/sok2 diploid strains form pseudohyphae at an accelerated rate, the Sok2 protein may inhibit the switch from unicellular to filamentous growth, a process that is dependent on cAMP. Thus, the product of SOK2 may act downstream of PKA to regulate the expression of genes important in growth and development.

[1]  D. D. Perkins Biochemical Mutants in the Smut Fungus Ustilago Maydis. , 1949, Genetics.

[2]  M. Grenson,et al.  Multiplicity of the amino acid permeases in Saccharomyces cerevisiae. IV. Evidence for a general amino acid permease. , 1966, Journal of bacteriology.

[3]  G C Johnston,et al.  Coordination of growth with cell division in the yeast Saccharomyces cerevisiae. , 1977, Experimental cell research.

[4]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[5]  G. Fink,et al.  Methods in yeast genetics , 1979 .

[6]  K. Matsumoto,et al.  Isolation and characterization of yeast mutants deficient in adenylate cyclase and cAMP-dependent protein kinase. , 1982, Proceedings of the National Academy of Sciences of the United States of America.

[7]  K. Murata,et al.  Transformation of intact yeast cells treated with alkali cations. , 1984, Journal of bacteriology.

[8]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[9]  A. Martinez-Arias,et al.  Beta-galactosidase gene fusions for analyzing gene expression in escherichia coli and yeast. , 1983, Methods in enzymology.

[10]  M. Wigler,et al.  Genetic analysis of yeast RAS1 and RAS2 genes , 1984, Cell.

[11]  M. Wigler,et al.  In yeast, RAS proteins are controlling elements of adenylate cyclase , 1985, Cell.

[12]  M. Wigler,et al.  Cloning and characterization of the high-affinity cAMP phosphodiesterase of Saccharomyces cerevisiae. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[13]  K. Tatchell,et al.  Characterization of Saccharomyces cerevisiae genes encoding subunits of cyclic AMP-dependent protein kinase , 1987, Molecular and cellular biology.

[14]  M. Wigler,et al.  Rigorous feedback control of cAMP levels in Saccharomyces cerevisiae. , 1987, Genes & development.

[15]  D. Botstein,et al.  A Saccharomyces cerevisiae genomic plasmid bank based on a centromere-containing shuttle vector. , 1987, Gene.

[16]  J. Broach,et al.  Fatty acylation is important but not essential for Saccharomyces cerevisiae RAS function , 1987, Molecular and cellular biology.

[17]  Michael Wigler,et al.  Three different genes in S. cerevisiae encode the catalytic subunits of the cAMP-dependent protein kinase , 1987, Cell.

[18]  R. D. Gietz,et al.  New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites. , 1988, Gene.

[19]  K. Matsumoto,et al.  Dual regulation of the expression of the polyubiquitin gene by cyclic AMP and heat shock in yeast. , 1988, The EMBO journal.

[20]  M. Wigler,et al.  cAMP-independent control of sporulation, glycogen metabolism, and heat shock resistance in S. cerevisiae , 1988, Cell.

[21]  M. Shepherd Morphogenetic transformation of fungi. , 1988, Current topics in medical mycology.

[22]  S. S. Smith,et al.  Quantitative evaluation of Escherichia coli host strains for tolerance to cytosine methylation in plasmid and phage recombinants. , 1989, Nucleic acids research.

[23]  Y. Nogi,et al.  Functional domains of a negative regulatory protein, GAL80, of Saccharomyces cerevisiae , 1989, Molecular and cellular biology.

[24]  Mutants of H‐ras that interfere with RAS effector function in Saccharomyces cerevisiae. , 1989, The EMBO journal.

[25]  A. Martinez-Arias,et al.  23 – β-Galactosidase Gene Fusions for Analyzing Gene Expression in Escherichia coli and Yeast , 1989 .

[26]  J. Broach,et al.  Loss of Ras activity in Saccharomyces cerevisiae is suppressed by disruptions of a new kinase gene, YAKI, whose product may act downstream of the cAMP-dependent protein kinase. , 1989, Genes & development.

[27]  C. Denis,et al.  Cyclic AMP-dependent protein kinase phosphorylates and inactivates the yeast transcriptional activator ADR1 , 1989, Cell.

[28]  R. Sikorski,et al.  A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. , 1989, Genetics.

[29]  James R. Broach,et al.  SRV2, a gene required for RAS activation of adenylate cyclase in yeast , 1990, Cell.

[30]  B. Kemp,et al.  Protein kinase recognition sequence motifs. , 1990, Trends in biochemical sciences.

[31]  J. Broach,et al.  The function of ras genes in Saccharomyces cerevisiae. , 1990, Advances in cancer research.

[32]  I. Herskowitz,et al.  Transcriptional activation of CLN1, CLN2, and a putative new G1 cyclin (HCS26) by SWI4, a positive regulator of G1-specific transcription. , 1991, Cell.

[33]  D. Shore,et al.  Separation of transcriptional activation and silencing functions of the RAP1-encoded repressor/activator protein 1: isolation of viable mutants affecting both silencing and telomere length. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[34]  J. Broach,et al.  RAS genes in Saccharomyces cerevisiae: signal transduction in search of a pathway. , 1991, Trends in genetics : TIG.

[35]  B. Kemp,et al.  Substrate specificities for yeast and mammalian cAMP-dependent protein kinases are similar but not identical. , 1991, The Journal of biological chemistry.

[36]  Brenda J. Andrews,et al.  Transcriptional activation of CLN1, CLN2, and a putative new G1 cyclin (HCS26) by SWI4, a positive regulator of G1-specific transcription , 1991, Cell.

[37]  K. Köhrer,et al.  Preparation of high molecular weight RNA. , 1991, Methods in enzymology.

[38]  Kim Nasmyth,et al.  The role of SWI4 and SWI6 in the activity of G1 cyclins in yeast , 1991, Cell.

[39]  J. Broach,et al.  The Saccharomyces cerevisiae YAK1 gene encodes a protein kinase that is induced by arrest early in the cell cycle , 1991, Molecular and cellular biology.

[40]  K. Arndt,et al.  SIT4 protein phosphatase is required for the normal accumulation of SWI4, CLN1, CLN2, and HCS26 RNAs during late G1. , 1992, Genes & development.

[41]  J. Broach,et al.  Inactivation of the protein phosphatase 2A regulatory subunit A results in morphological and transcriptional defects in Saccharomyces cerevisiae , 1992, Molecular and cellular biology.

[42]  Gerald R. Fink,et al.  Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: Regulation by starvation and RAS , 1992, Cell.

[43]  Michael Primig,et al.  Anatomy of a transcription factor important for the Start of the cell cycle in Saccharomyces cerevisiae , 1992, Nature.

[44]  K. Tatchell,et al.  GAC1 may encode a regulatory subunit for protein phosphatase type 1 in Saccharomyces cerevisiae. , 1992, The EMBO journal.

[45]  R. Kay,et al.  Mutation of protein kinase A causes heterochronic development of Dictyostelium , 1992, Nature.

[46]  B. Kemp,et al.  ADR1c mutations enhance the ability of ADR1 to activate transcription by a mechanism that is independent of effects on cyclic AMP-dependent protein kinase phosphorylation of Ser-230 , 1992, Molecular and cellular biology.

[47]  S. Dorland,et al.  Parallel pathways of gene regulation: homologous regulators SWI5 and ACE2 differentially control transcription of HO and chitinase. , 1992, Genes & development.

[48]  Jianguo Wu,et al.  StuA is required for cell pattern formation in Aspergillus. , 1992, Genes & development.

[49]  D. Kalderon,et al.  Genetic investigation of cAMP-dependent protein kinase function in Drosophila development. , 1993, Genes & development.

[50]  K. Nasmyth,et al.  A role for the transcription factors Mbp1 and Swi4 in progression from G1 to S phase. , 1993, Science.

[51]  M. Olson,et al.  Physical maps of the six smallest chromosomes of Saccharomyces cerevisiae at a resolution of 2.6 kilobase pairs. , 1993, Genetics.

[52]  W. Heideman,et al.  Connections between the Ras-cyclic AMP pathway and G1 cyclin expression in the budding yeast Saccharomyces cerevisiae , 1993, Molecular and cellular biology.

[53]  L. C. Robinson,et al.  Casein kinase I-like protein kinases encoded by YCK1 and YCK2 are required for yeast morphogenesis , 1993, Molecular and cellular biology.

[54]  C. Mazzoni,et al.  The SLT2 (MPK1) MAP kinase homolog is involved in polarized cell growth in Saccharomyces cerevisiae , 1993, The Journal of cell biology.

[55]  L. Guarente Synthetic enhancement in gene interaction: a genetic tool come of age. , 1993, Trends in genetics : TIG.

[56]  G. Adam,et al.  A Saccharomyces cerevisiae UAS element controlled by protein kinase A activates transcription in response to a variety of stress conditions. , 1993, The EMBO journal.

[57]  The yeast and mammalian Ras pathways control transcription of heat shock genes independently of heat shock transcription factor. , 1994, Molecular and cellular biology.

[58]  M. Ward,et al.  The Yak1 protein kinase of Saccharomyces cerevisiae moderates thermotolerance and inhibits growth by an Sch9 protein kinase-independent mechanism. , 1994, Genetics.

[59]  E. Lalli,et al.  Signal transduction and gene regulation: the nuclear response to cAMP. , 1994, The Journal of biological chemistry.

[60]  G. Fink,et al.  Induction of pseudohyphal growth by overexpression of PHD1, a Saccharomyces cerevisiae gene related to transcriptional regulators of fungal development , 1994, Molecular and cellular biology.

[61]  K. Struhl,et al.  Protein kinase A mediates growth-regulated expression of yeast ribosomal protein genes by modulating RAP1 transcriptional activity , 1994, Molecular and Cellular Biology.

[62]  L. Alberghina,et al.  Repression of growth-regulated Gl cyclin expression by cyclic AMP in budding yeast , 1994, Nature.

[63]  M. Ward,et al.  Suppression of a yeast cyclic AMP-dependent protein kinase defect by overexpression of SOK1, a yeast gene exhibiting sequence similarity to a developmentally regulated mouse gene , 1994, Molecular and cellular biology.

[64]  M. Tyers,et al.  Inhibition of G1 cyclin activity by Ras/cAMP pathway in yeast , 1994 .

[65]  S. Gold,et al.  cAMP regulates morphogenesis in the fungal pathogen Ustilago maydis. , 1994, Genes & development.

[66]  K. Struhl,et al.  The UV response involving the ras signaling pathway and AP-1 transcription factors is conserved between yeast and mammals , 1994, Cell.

[67]  J. Broach,et al.  Nutrient availability and the RAS/cyclic AMP pathway both induce expression of ribosomal protein genes in Saccharomyces cerevisiae but by different mechanisms , 1995, Molecular and cellular biology.