Regulation of Cdc25C by ERK-MAP kinases during the G2/M transition.
Induction of G(2)/M phase transition in mitotic and meiotic cell cycles requires activation by phosphorylation of the protein phosphatase Cdc25. Although Cdc2/cyclin B and polo-like kinase (PLK) can phosphorylate and activate Cdc25 in vitro, phosphorylation by these two kinases is insufficient to account for Cdc25 activation during M phase induction. Here we demonstrate that p42 MAP kinase (MAPK), the Xenopus ortholog of ERK2, is a major Cdc25 phosphorylating kinase in extracts of M phase-arrested Xenopus eggs. In Xenopus oocytes, p42 MAPK interacts with hypophosphorylated Cdc25 before meiotic induction. During meiotic induction, p42 MAPK phosphorylates Cdc25 at T48, T138, and S205, increasing Cdc25's phosphatase activity. In a mammalian cell line, ERK1/2 interacts with Cdc25C in interphase and phosphorylates Cdc25C at T48 in mitosis. Inhibition of ERK activation partially inhibits T48 phosphorylation, Cdc25C activation, and mitotic induction. These findings demonstrate that ERK-MAP kinases are directly involved in activating Cdc25 during the G(2)/M transition.
Wang
Ruoning
R
Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
He
Guangan
G
Nelman-Gonzalez
Mayra
M
Ashorn
Cheryl L
CL
Gallick
Gary E
GE
Stukenberg
P Todd
PT
Kirschner
Marc W
MW
Kuang
Jian
J
D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D007399:Interphase; D008540:Meiosis; D019950:Mitogen-Activated Protein Kinase 1 / Q000737:chemistry / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D008938:Mitosis; D008969:Molecular Sequence Data; D009865:Oocytes / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D016415:Sequence Alignment; D014981:Xenopus; D029867:Xenopus Proteins / Q000737:chemistry / Q000378:metabolism*; D020687:cdc25 Phosphatases / Q000378:metabolism*
D018797:Cell Cycle Proteins; D029867:Xenopus Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C448499:p42 MAP kinase, Xenopus; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases