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A link between MAP kinase and p34 cdc2 /cyclin B during oocyte maturation: p90 rsk phosphorylates and inactivates the p34 cdc2 inhibitory kinase Myt1
Author(s) -
Palmer Amparo,
Gavin AnneClaude,
Nebreda Angel R.
Publication year - 1998
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/17.17.5037
Subject(s) - biology , cyclin dependent kinase 1 , microbiology and biotechnology , cyclin b , cyclin dependent kinase , phosphorylation , maturation promoting factor , kinase , wee1 , cyclin , cell cycle , biochemistry , cell
M‐phase entry in eukaryotic cells is driven by activation of MPF, a regulatory factor composed of cyclin B and the protein kinase p34 cdc2 . In G 2 ‐arrested Xenopus oocytes, there is a stock of p34 cdc2 /cyclin B complexes (pre‐MPF) which is maintained in an inactive state by p34 cdc2 phosphorylation on Thr14 and Tyr15. This suggests an important role for the p34 cdc2 inhibitory kinase(s) such as Wee1 and Myt1 in regulating the G 2 →M transition during oocyte maturation. MAP kinase (MAPK) activation is required for M‐phase entry in Xenopus oocytes, but its precise contribution to the activation of pre‐MPF is unknown. Here we show that the C‐terminal regulatory domain of Myt1 specifically binds to p90 rsk , a protein kinase that can be phosphorylated and activated by MAPK. p90 rsk in turn phosphorylates the C‐terminus of Myt1 and down‐regulates its inhibitory activity on p34 cdc2 /cyclin B in vitro . Consistent with these results, Myt1 becomes phosphorylated during oocyte maturation, and activation of the MAPK–p90 rsk cascade can trigger some Myt1 phosphorylation prior to pre‐MPF activation. We found that Myt1 preferentially associates with hyperphosphorylated p90 rsk , and complexes can be detected in immunoprecipitates from mature oocytes. Our results suggest that during oocyte maturation MAPK activates p90 rsk and that p90 rsk in turn down‐regulates Myt1, leading to the activation of p34 cdc2 /cyclin B.