Novel Sensing Mechanisms and Targets for the cAMP-protein Kinase A Pathway in the Yeast Saccharomyces Cerevisiae

Mol Microbiol. 1999 Sep;33(5):904-18. doi: 10.1046/j.1365-2958.1999.01538.x.

Abstract

The cAMP-protein kinase A (PKA) pathway in the yeast Saccharomyces cerevisiae plays a major role in the control of metabolism, stress resistance and proliferation, in particular in connection with the available nutrient conditions. Extensive information has been obtained on the core section of the pathway, i.e. Cdc25, Ras, adenylate cyclase, PKA, and on components interacting directly with this core section, such as the Ira proteins, Cap/Srv2 and the two cAMP phosphodiesterases. Recent work has now started to reveal upstream regulatory components and downstream targets of the pathway. A G-protein-coupled receptor system (Gpr1-Gpa2) acts upstream of adenylate cyclase and is required for glucose activation of cAMP synthesis in concert with a glucose phosphorylation-dependent mechanism. Although a genuine signalling role for the Ras proteins remains unclear, they appear to mediate at least part of the potent stimulation of cAMP synthesis by intracellular acidification. Recently, several new targets of the PKA pathway have been discovered. These include the Msn2 and Msn4 transcription factors mediating part of the induction of STRE-controlled genes by a variety of stress conditions, the Rim15 protein kinase involved in stationary phase induction of a similar set of genes and the Pde1 low-affinity cAMP phosphodiesterase, which specifically controls agonist-induced cAMP signalling. A major issue that remains to be resolved is the precise connection between the cAMP-PKA pathway and other nutrient-regulated components involved in the control of growth and of phenotypic characteristics correlated with growth, such as the Sch9 and Yak1 protein kinases. Cln3 appears to play a crucial role in the connection between the availability of certain nutrients and Cdc28 kinase activity, but it remains to be clarified which nutrient-controlled pathways control Cln3 levels.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / genetics
  • 3',5'-Cyclic-AMP Phosphodiesterases / metabolism
  • 3',5'-Cyclic-GMP Phosphodiesterases / genetics
  • 3',5'-Cyclic-GMP Phosphodiesterases / metabolism
  • Adenylyl Cyclases / metabolism
  • Cyclic AMP / metabolism*
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Cyclic Nucleotide Phosphodiesterases, Type 1
  • Fungal Proteins / metabolism
  • GTP-Binding Protein alpha Subunits*
  • GTP-Binding Proteins / metabolism
  • Glucose / metabolism
  • Heterotrimeric GTP-Binding Proteins*
  • Molecular Sequence Data
  • Phosphoric Diester Hydrolases*
  • Receptors, Cell Surface / metabolism*
  • Receptors, G-Protein-Coupled*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Signal Transduction
  • Transcription, Genetic
  • ras Proteins / metabolism

Substances

  • Fungal Proteins
  • GPR1 protein, S cerevisiae
  • GTP-Binding Protein alpha Subunits
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • Saccharomyces cerevisiae Proteins
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Phosphoric Diester Hydrolases
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 1
  • 3',5'-Cyclic-GMP Phosphodiesterases
  • GTP-Binding Proteins
  • Gpa2 protein, S cerevisiae
  • Heterotrimeric GTP-Binding Proteins
  • ras Proteins
  • Adenylyl Cyclases
  • Glucose