TY - JOUR
T1 - Regulation of Cdc25C by ERK-MAP Kinases during the G2/M Transition
AU - Wang, Ruoning
AU - He, Guangan
AU - Nelman-Gonzalez, Mayra
AU - Ashorn, Cheryl L.
AU - Gallick, Gary E.
AU - Stukenberg, P. Todd
AU - Kirschner, Marc W.
AU - Kuang, Jian
N1 - Funding Information:
This paper is dedicated to the late Laurence D. Etkin for his consistent encouragement and support of this project through the years. This work was supported by NIH/NCI grant RO1 CA93941 awarded to J. Kuang. DNA sequencing was performed by the DNA Analysis Facility of UT M. D. Anderson Cancer Center supported by NCI Grant CA-16672. We thank Drs. T. Hunt and A. R. Nebreda for providing bacterial expression vectors for GST-Cdc25, GST-Cdc25N1, MBP-MAPK, and MBP-MEK1-CA; Dr. W. Dunphy for providing polyclonal antibodies that recognized Xenopus Cdc25 and Plx1; Dr. J. Ferrell for providing vectors for myc-XCL100 and His-xWee1 A, rabbit immune serum against p42 MAPK; Dr. H. Kobayashi for providing vector for myc-Cdc2AF; Dr. J. Frost for providing vector for HA-ERK2 and CA-MEK1; Dr. S. Kornbluth for providing anti-pT138 antibody; and Dr. J. Maller for providing the baculovirus for constitutively activated His-tagged Plx1.
PY - 2007/3/23
Y1 - 2007/3/23
N2 - Induction of G2/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 G2/M transition.
AB - Induction of G2/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 G2/M transition.
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U2 - 10.1016/j.cell.2006.11.053
DO - 10.1016/j.cell.2006.11.053
M3 - Article
C2 - 17382881
AN - SCOPUS:33947322004
SN - 0092-8674
VL - 128
SP - 1119
EP - 1132
JO - Cell
JF - Cell
IS - 6
ER -