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GSK‐3 kinase Mck1 and calcineurin coordinately mediate Hsl1 down‐regulation by Ca 2+ in budding yeast
Author(s) -
Mizunuma Masaki,
Hirata Dai,
Miyaoka Rie,
Miyakawa Tokichi
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.5.1074
Subject(s) - biology , calcineurin , microbiology and biotechnology , cyclin dependent kinase 1 , casein kinase 1 , protein kinase a , signal transduction , kinase , ask1 , ubiquitin ligase , cyclin dependent kinase 2 , biochemistry , cell cycle , ubiquitin , cell , gene , medicine , surgery , transplantation
The Ca 2+ ‐activated pathways of Saccharomyces cerevisiae induce a delay in the onset of mitosis through the activation of Swe1, a negative regulatory kinase that inhibits the Cdc28–Clb complex. Calcineurin and Mpk1 activate Swe1 at the transcriptional and post‐translational level, respectively, and both pathways are essential for the cell cycle delay. Our genetic screening identified the MCK1 gene, which encodes a glycogen synthetase kinase‐3 family protein kinase, as a component of the Ca 2+ signaling pathway. Genetic analyses indicated that Mck1 functions downstream of the Mpk1 pathway and down‐regulates Hsl1, an inhibitory kinase of Swe1. In medium with a high concentration of Ca 2+ , Hsl1 was delocalized from the bud neck and destabilized in a manner dependent on both calcineurin and Mck1. Calcineurin was required for the dephosphorylation of autophosphorylated Hsl1. The E3 ubiquitin ligase complex SCF Cdc4 , but not the anaphase‐promoting complex (APC), was essential for Hsl1 destabilization. The Ca 2+ ‐activated pathway may play a role in the rapid inactivation of Hsl1 at the cell cycle stage(s) when APC activity is low.