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Novel sensing mechanisms and targets for the cAMP–protein kinase A pathway in the yeast Saccharomyces cerevisiae
Author(s) -
Thevelein Johan M.,
De Winde Johannes H.
Publication year - 1999
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1046/j.1365-2958.1999.01538.x
Subject(s) - biology , protein kinase a , camp dependent pathway , saccharomyces cerevisiae , biochemistry , adenylate kinase , second messenger system , signal transduction , microbiology and biotechnology , creb1 , g protein coupled receptor , cyclase , phosphodiesterase , kinase , transcription factor , yeast , receptor , gene , enzyme , creb
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.