Phosphorylation by Pho85 Cyclin-dependent Kinase Acts as a Signal for the Down-regulation of the Yeast Sphingoid Long-chain Base Kinase Lcb4 during the Stationary Phase

作者: Soichiro Iwaki , Akio Kihara , Takamitsu Sano , Yasuyuki Igarashi

DOI: 10.1074/JBC.M410908200

关键词: Cyclin-dependent kinase complexASK1Cell biologyPhosphorylation cascadeMitogen-activated protein kinase kinaseBiochemistryBiologyCyclin-dependent kinaseCyclin-dependent kinase 2Cyclin-dependent kinase 1MAP2K7

摘要: Sphingoid long-chain base 1-phosphates (LCBPs) act as bioactive lipid molecules in eukaryotic cells. In yeast, LCBPs are synthesized mainly by the kinase Lcb4p. Until now, regulatory mechanism for Lcb4p has been unclear. present study, we found that is post-translationally modified phosphorylation. Using a protein mutant yeast collection, further demonstrated cyclin-dependent Pho85p involved this functions number of cellular processes, especially response to environmental changes. Two 10 cyclins, Pcl1p and Pcl2p had overlapping phosphorylation Site-directed mutagenesis identified sites Ser(451) Ser(455). Additionally, pulse-chase experiments revealed degraded via ubiquitin-dependent pathway. The was stabilized Deltapho85 cells, suggesting acts signal degradation. down-regulated stationary phase cell growth, both ubiquitination appear be important process. Moreover, delivered vacuole degradation multivesicular body. Since forced accumulation results prolonged growth during phase, down-regulation may physiologically proper responses nutrient deprivation.

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