Activation of Srk1 by the mitogen-activated protein kinase Sty1/Spc1 precedes its dissociation from the kinase and signals its degradation.
Control of cell cycle progression by stress-activated protein kinases (SAPKs) is essential for cell adaptation to extracellular stimuli. The Schizosaccharomyces pombe SAPK Sty1/Spc1 orchestrates general changes in gene expression in response to diverse forms of cytotoxic stress. Here we show that Sty1/Spc1 is bound to its target, the Srk1 kinase, when the signaling pathway is inactive. In response to stress, Sty1/Spc1 phosphorylates Srk1 at threonine 463 of the regulatory domain, inducing both activation of Srk1 kinase, which negatively regulates cell cycle progression by inhibiting Cdc25, and dissociation of Srk1 from the SAPK, which leads to Srk1 degradation by the proteasome.
López-Avilés
Sandra
S
Departament de Biologia Cellular, Universitat de Barcelona. Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Catalunya, Spain.
Lambea
Eva
E
Moldón
Alberto
A
Grande
Maribel
M
Fajardo
Alba
A
Rodríguez-Gabriel
Miguel A
MA
Hidalgo
Elena
E
Aligue
Rosa
R
D021581:Active Transport, Cell Nucleus; D019943:Amino Acid Substitution; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D004795:Enzyme Stability; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012568:Schizosaccharomyces / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013912:Threonine / Q000737:chemistry; D020666:ras-GRF1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D005656:Fungal Proteins; D011993:Recombinant Fusion Proteins; D029702:Schizosaccharomyces pombe Proteins; D020666:ras-GRF1; D013912:Threonine; C499611:SRK1 protein, S pombe; D020928:Mitogen-Activated Protein Kinases; C524689:Spc1 protein, S pombe; C095409:sty1 protein, S pombe; D046988:Proteasome Endopeptidase Complex