User:Ilya/Yeast/Mating pheromone response pathway

Components

• GPCR
• Ras

Miscellaneous

• Crosstalk in the pathways is eliminated by formation of pathway-specific complexes (Ste5:Ste11:Ste7:Fus3, Pbs2:Ste11:Hog1)

Pheromone processing genes

• STE14
  • carries out C-terminal methylation of prenylated proteins including a-factor, Ras1p, and Ras2p
  • encodes the prenylcysteine-dependent carboxyl methyltransferase that mediates methylation, the final step in modification of CAAX proteins; Ste14p is also membrane associated

Yeast. 1993 Aug;9(8):907-13

• STE13
• AXL1
• STE23
• RAM1
• RAM2
• STE24
• RCE1
• KEX2
• KEX1
• STE23

Ste13 Dipeptidyl aminopeptidase A involved in maturation of a-factor

AXL1 Protease involved in proteolytic step of a-factor N-terminal processing

Ram1, Ram2 Required for a-factor prenylation

Swe1 Protein kinase that regulates the G2/M transition by inhibition of Cdc28p kinase activity

Ras1 - pombe homolog interacts with MAPKKK

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SAG1 (α-agglutinin) provides tight cellcell adhesion during mating in S. cerevisiae.

FUS1 Protein with SH3 domain required for cell fusion during mating, located at the tip of the mating projection

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The Saccharomyces cerevisiae mating pheromone a-factor is a prenylated and carboxyl methylated extracellular peptide signaling molecule.

Like the peptide hormones secreted by higher eukaryotes, the yeast mating pheromones are initially synthesized as larger precursors that undergo posttranslational modification and proteolytic processing before their export from the cell. Despite their functional equivalence as signaling molecules, the a-factor and alpha-factor pheromones are structurally quite dissimilar and exemplify distinct paradigms for biogenesis.

The maturation of alpha-factor is well characterized and involves the classical secretory pathway (ER -> Golgi -> secretory vesicles). Subsequent to its translocation across the ER membrane, the alpha-factor precursor undergoes signal sequence cleavage, glycosylation, a series of proteolytic processing steps in the lumenal compartments of the secretory pathway, and then exits the cell via exocytosis. In contrast to our extensive understanding of alpha-factor maturation, our view of the events involved in a-factor biogenesis is still incomplete. An important difference between the two pheromones is that secretion of a-factor is mediated by a nonclassical export mechanism. Mature bioactive a-factor is a prenylated and methylated dodecapeptide, derived by the posttranslational maturation of a precursor encoded by the similar and functionally redundant genes MFA1 and MFA2. The COOH-terminal maturation of the a-factor precursor is directed by its CAAX sequence. The a-factor precursor can be subdivided into three functional segments: (a) the mature portion, which is ultimately secreted; (b) the NH2-terminal extension; (c) the COOH-terminal CAAX motif. biogenesis of a-factor occurs by an ordered series of events involving first COOH-terminal CAAX modification, then NH2-terminal processing, and finally export from the cell (He et al., 1991; Michaelis, 1993; Sapperstein et al., 1994). In mutants (ram1, ram2, and ste14) defective in CAAX modification, biologically active a-factor is not produced.

J Cell Biol 136(2):251-69

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In S. cerevisiae, meiosis is initiated only by diploid cells deprived of glucose and nitrogen and grown in the presence of a nonfermentable carbon source,

PNAS USA 98:3249-3253

References

• Pathway architecture overview

1. Kofahl B and Klipp E. Modelling the dynamics of the yeast pheromone pathway. Yeast. 2004 Jul 30;21(10):831-50. DOI:10.1002/yea.1122 |
2. Banuett F. Signalling in the yeasts: an informational cascade with links to the filamentous fungi. Microbiol Mol Biol Rev. 1998 Jun;62(2):249-74. DOI:10.1128/MMBR.62.2.249-274.1998 |
3. Bardwell L. A walk-through of the yeast mating pheromone response pathway. Peptides. 2004 Sep;25(9):1465-76. DOI:10.1016/j.peptides.2003.10.022 |