Pheromone Response in Yeast: Association of Bem1p with Proteins of the MAP Kinase Cascade and Actin

Haploid cells of the yeast Saccharomyces cerevisiae respond to mating pheromones with polarized growth toward the mating partner. This morphological response requires the function of the cell polarity establishment protein Bem1p. Immunochemical and two-hybrid protein interaction assays revealed that Bem1p interacts with two components of the pheromone-responsive mitogen-activated protein (MAP) kinase cascade, Ste20p and Ste5p, as well as with actin. Mutants of Bem1p that are associated with defective pheromone-induced polarized morphogenesis interacted with Ste5p and actin but not with Ste20p. Thus, the association of Bem1p with Ste20p and Ste5p may contribute to the conveyance of spatial information that regulates polarized rearrangement of the actin cytoskeleton during yeast mating.

[1]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[2]  L. Hartwell,et al.  Regulation of mating in the cell cycle of Saccharomyces cerevisiae , 1977, The Journal of cell biology.

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

[4]  J. Pringle,et al.  A mutant of yeast defective in cellular morphogenesis. , 1978, Science.

[5]  C. Slayman,et al.  The effects of vanadate on the plasma membrane ATPase of Neurospora crassa. , 1979, The Journal of biological chemistry.

[6]  R. Schekman,et al.  Localized secretion of acid phosphatase reflects the pattern of cell surface growth in saccharomyces cerevisiae , 1980, The Journal of cell biology.

[7]  J. Pringle,et al.  Roles of the CDC24 gene product in cellular morphogenesis during the Saccharomyces cerevisiae cell cycle , 1981, The Journal of cell biology.

[8]  S. Fuller,et al.  Cell surface polarity in epithelia. , 1985, Annual review of cell biology.

[9]  G. Gerisch Cyclic AMP and other signals controlling cell development and differentiation in Dictyostelium. , 1987, Annual review of biochemistry.

[10]  P. Devreotes,et al.  Chemotaxis in eukaryotic cells: a focus on leukocytes and Dictyostelium. , 1988, Annual review of cell biology.

[11]  D. Bray,et al.  Growth cone motility and guidance. , 1988, Annual review of cell biology.

[12]  E. Rodriguez-Boulan,et al.  Morphogenesis of the polarized epithelial cell phenotype. , 1989, Science.

[13]  P. Orlean,et al.  Topography of glycosylation in yeast: characterization of GDPmannose transport and lumenal guanosine diphosphatase activities in Golgi-like vesicles. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[14]  S. Fields,et al.  A novel genetic system to detect protein–protein interactions , 1989, Nature.

[15]  J. Pringle,et al.  Molecular characterization of CDC42, a Saccharomyces cerevisiae gene involved in the development of cell polarity , 1990, The Journal of cell biology.

[16]  J. Pringle,et al.  CDC42 and CDC43, two additional genes involved in budding and the establishment of cell polarity in the yeast Saccharomyces cerevisiae , 1990, The Journal of cell biology.

[17]  I. Herskowitz,et al.  Genetic control of bud site selection in yeast by a set of gene products that constitute a morphogenetic pathway , 1991, Cell.

[18]  I. Herskowitz,et al.  Yeast BUD5, encoding a putative GDP-GTP exchange factor, is necessary for bud site selection and interacts with bud formation gene BEM1 , 1991, Cell.

[19]  J. Pringle,et al.  Use of a screen for synthetic lethal and multicopy suppressee mutants to identify two new genes involved in morphogenesis in Saccharomyces cerevisiae , 1991, Molecular and cellular biology.

[20]  S. Fields,et al.  The two-hybrid system: a method to identify and clone genes for proteins that interact with a protein of interest. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[21]  I. Herskowitz,et al.  A yeast gene (BEM1) necessary for cell polarization whose product contains two SH3 domains , 1992, Nature.

[22]  Anne J. Ridley,et al.  The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors , 1992, Cell.

[23]  Anne J. Ridley,et al.  The small GTP-binding protein rac regulates growth factor-induced membrane ruffling , 1992, Cell.

[24]  M. Whiteway,et al.  The protein kinase homologue Ste20p is required to link the yeast pheromone response G‐protein beta gamma subunits to downstream signalling components. , 1992, The EMBO journal.

[25]  J. Segall,et al.  Polarization of yeast cells in spatial gradients of alpha mating factor. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[26]  D. Botstein,et al.  Subcellular localization of Cdc42p, a Saccharomyces cerevisiae GTP-binding protein involved in the control of cell polarity. , 1993, Molecular biology of the cell.

[27]  R. W. Davis,et al.  A dominant truncation allele identifies a gene, STE20, that encodes a putative protein kinase necessary for mating in Saccharomyces cerevisiae. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[28]  Jonathan A. Cooper,et al.  Mammalian Ras interacts directly with the serine/threonine kinase raf , 1993, Cell.

[29]  G. Downey Mechanisms of leukocyte motility and chemotaxis. , 1994, Current opinion in immunology.

[30]  I. Herskowitz,et al.  Identification of genes required for normal pheromone-induced cell polarization in Saccharomyces cerevisiae. , 1994, Genetics.

[31]  M. Wigler,et al.  Complexes between STE5 and components of the pheromone-responsive mitogen-activated protein kinase module. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[32]  E. Elion,et al.  Ste5 tethers multiple protein kinases in the MAP kinase cascade required for mating in S. cerevisiae , 1994, Cell.

[33]  J. Chenevert,et al.  Cell polarization directed by extracellular cues in yeast. , 1994, Molecular biology of the cell.

[34]  L. Lim,et al.  A brain serine/threonine protein kinase activated by Cdc42 and Rac1 , 1994, Nature.

[35]  R. Cerione,et al.  Interactions between the bud emergence proteins Bem1p and Bem2p and Rho- type GTPases in yeast , 1994, The Journal of cell biology.

[36]  G. Sprague,,et al.  Protein-protein interactions in the yeast pheromone response pathway: Ste5p interacts with all members of the MAP kinase cascade. , 1994, Genetics.

[37]  J. Chant,et al.  GTPase cascades choreographing cellular behavior: Movement, morphogenesis, and more , 1995, Cell.

[38]  M. Karin,et al.  Selective activation of the JNK signaling cascadeand c-Jun transcriptional activity by the small GTPases Rac and Cdc42Hs , 1995, Cell.

[39]  S. Reed,et al.  Role for the Rho-family GTPase Cdc42 in yeast mating-pheromone signal pathway , 1995, Nature.

[40]  K. Clark,et al.  Association of the yeast pheromone response G protein beta gamma subunits with the MAP kinase scaffold Ste5p. , 1995, Science.

[41]  P. Crespo,et al.  The small GTP-binding proteins Rac1 and Cdc42regulate the activity of the JNK/SAPK signaling pathway , 1995, Cell.

[42]  D. Y. Thomas,et al.  Saccharomyces cerevisiae CNE1 Encodes an Endoplasmic Reticulum (ER) Membrane Protein with Sequence Similarity to Calnexin and Calreticulin and Functions as a Constituent of the ER Quality Control Apparatus (*) , 1995, The Journal of Biological Chemistry.

[43]  L. Lim,et al.  The Ras-related protein Cdc42Hs and bradykinin promote formation of peripheral actin microspikes and filopodia in Swiss 3T3 fibroblasts , 1995, Molecular and cellular biology.

[44]  C. Nobes,et al.  Rho, Rac, and Cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia , 1995, Cell.

[45]  I. Herskowitz MAP kinase pathways in yeast: For mating and more , 1995, Cell.

[46]  M. Whiteway,et al.  Molecular Characterization of Ste20p, a Potential Mitogen-activated Protein or Extracellular Signal-regulated Kinase Kinase (MEK) Kinase Kinase from Saccharomyces cerevisiae(*) , 1995, The Journal of Biological Chemistry.