PAS kinase promotes cell survival and growth through activation of Rho1

Sci Signal. 2012 Jan 31;5(209):ra9. doi: 10.1126/scisignal.2002435.

Abstract

In Saccharomyces cerevisiae, phosphorylation of Ugp1 by either of the yeast PASK family protein kinases (yPASK), Psk1 or Psk2, directs this metabolic enzyme to deliver glucose to the periphery for synthesis of the cell wall. However, we isolated PSK1 and PSK2 in a high-copy suppressor screen of a temperature-sensitive mutant of target of rapamycin 2 (TOR2). Posttranslational activation of yPASK, either by cell integrity stress or by growth on nonfermentative carbon sources, also suppressed the growth defect resulting from tor2 mutation. Although suppression of the tor2 mutant growth phenotype by activation of the kinase activity of yPASK required phosphorylation of the metabolic enzyme Ugp1 on serine 11, this resulted in the formation of a complex that induced Rho1 activation, rather than required the glucose partitioning function of Ugp1. In addition to phosphorylated Ugp1, this complex contained Rom2, a Rho1 guanine nucleotide exchange factor, and Ssd1, an mRNA-binding protein. Activation of yPASK-dependent Ugp1 phosphorylation, therefore, enables two processes that are required for cell growth and stress resistance: synthesis of the cell wall through partitioning glucose to the periphery and the formation of the signaling complex with Rom2 and Ssd1 to promote Rho1-dependent polarized cell growth. This complex may integrate metabolic and signaling responses required for cell growth and survival in suboptimal conditions.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Enzyme Activation / genetics
  • Glucose / genetics
  • Glucose / metabolism
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mutation
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinases / genetics
  • Protein Kinases / metabolism*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Saccharomyces cerevisiae / enzymology
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction / physiology*
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • Guanine Nucleotide Exchange Factors
  • Intracellular Signaling Peptides and Proteins
  • ROM2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Ssd1 protein, S cerevisiae
  • Protein Kinases
  • PSK1 protein, S cerevisiae
  • TOR2 protein, S cerevisiae
  • PSK2 protein, S cerevisiae
  • Protein Serine-Threonine Kinases
  • RHO1 protein, S cerevisiae
  • rho GTP-Binding Proteins
  • Glucose