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Mol Cell Biol
1994 Nov 01;1411:7265-75. doi: 10.1128/mcb.14.11.7265-7275.1994.
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Activation of cyclin-dependent kinase 4 (cdk4) by mouse MO15-associated kinase.
Matsuoka M
,
Kato JY
,
Fisher RP
,
Morgan DO
,
Sherr CJ
.
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The assembly of functional holoenzymes composed of regulatory D-type cyclins and cyclin-dependent kinases (cdks) is rate limiting for progression through the G1 phase of the mammalian somatic cell cycle. Complexes between D-type cyclins and their major catalytic subunit, cdk4, are catalytically inactive until cyclin-bound cdk4 undergoes phosphorylation on a single threonyl residue (Thr-172). This step is catalyzed by a cdk-activating kinase (CAK) functionally analogous to the enzyme which phosphorylates cdc2 and cdk2 at Thr-161/160. Here, we demonstrate that the catalytic subunit of mouse cdc2/cdk2 CAK (a 39-kDa protein designated p39MO15) can assemble with a regulatory protein present in either insect or mammalian cells to generate a CAK activity capable of phosphorylating and enzymatically activating both cdk2 and cdk4 in complexes with their respective cyclin partners. A newly identified 37-kDa cyclin-like protein (cyclin H [R. P. Fisher and D. O. Morgan, Cell 78:713-724, 1994]) can assemble with p39MO15 to activate both cyclin A-cdk2 and cyclin D-cdk4 in vitro, implying that CAK is structurally reminiscent of cyclin-cdk complexes themselves. Antisera produced to the p39MO15 subunit can completely deplete mammalian cell lysates of CAK activity for both cyclin A-cdk2 and cyclin D-cdk4, with recovery of activity in the resulting immune complexes. By using an immune complex CAK assay, CAK activity for cyclin A-cdk2 and cyclin D-cdk4 was detected both in quiescent cells and invariantly throughout the cell cycle. Therefore, although it is essential for the enzymatic activation of cyclin-cdk complexes, CAK appears to be neither rate limiting for the emergence of cells from quiescence nor subject to upstream regulatory control by stimulatory mitogens.
Anderson,
Subcellular localization of glycoproteins encoded by the viral oncogene v-fms.
1984, Pubmed
Anderson,
Subcellular localization of glycoproteins encoded by the viral oncogene v-fms.
1984,
Pubmed
Baldin,
Cyclin D1 is a nuclear protein required for cell cycle progression in G1.
1993,
Pubmed
Bates,
CDK6 (PLSTIRE) and CDK4 (PSK-J3) are a distinct subset of the cyclin-dependent kinases that associate with cyclin D1.
1994,
Pubmed
Booher,
Site-specific mutagenesis of cdc2+, a cell cycle control gene of the fission yeast Schizosaccharomyces pombe.
1986,
Pubmed
Connell-Crowley,
Phosphorylation independent activation of human cyclin-dependent kinase 2 by cyclin A in vitro.
1993,
Pubmed
,
Xenbase
De Bondt,
Crystal structure of cyclin-dependent kinase 2.
1993,
Pubmed
Desai,
Activation of human cyclin-dependent kinases in vitro.
1992,
Pubmed
Devault,
Cyclin A potentiates maturation-promoting factor activation in the early Xenopus embryo via inhibition of the tyrosine kinase that phosphorylates cdc2.
1992,
Pubmed
,
Xenbase
Downing,
Ligand-induced tyrosine kinase activity of the colony-stimulating factor 1 receptor in a murine macrophage cell line.
1988,
Pubmed
Ducommun,
cdc2 phosphorylation is required for its interaction with cyclin.
1991,
Pubmed
,
Xenbase
Dulić,
Association of human cyclin E with a periodic G1-S phase protein kinase.
1992,
Pubmed
Elledge,
CDK2 encodes a 33-kDa cyclin A-associated protein kinase and is expressed before CDC2 in the cell cycle.
1992,
Pubmed
,
Xenbase
Fesquet,
The MO15 gene encodes the catalytic subunit of a protein kinase that activates cdc2 and other cyclin-dependent kinases (CDKs) through phosphorylation of Thr161 and its homologues.
1993,
Pubmed
,
Xenbase
Fisher,
A novel cyclin associates with MO15/CDK7 to form the CDK-activating kinase.
1994,
Pubmed
Fleig,
A dominant negative allele of p34cdc2 shows altered phosphoamino acid content and sequesters p56cdc13 cyclin.
1992,
Pubmed
Gould,
Phosphorylation at Thr167 is required for Schizosaccharomyces pombe p34cdc2 function.
1991,
Pubmed
Gu,
Cell cycle regulation of CDK2 activity by phosphorylation of Thr160 and Tyr15.
1992,
Pubmed
Hartwell,
Checkpoints: controls that ensure the order of cell cycle events.
1989,
Pubmed
Jiang,
Overexpression of cyclin D1 in rat fibroblasts causes abnormalities in growth control, cell cycle progression and gene expression.
1993,
Pubmed
Kato,
Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4.
1993,
Pubmed
Kato,
Inhibition of granulocyte differentiation by G1 cyclins D2 and D3 but not D1.
1993,
Pubmed
Kato,
Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase.
1994,
Pubmed
Koff,
Formation and activation of a cyclin E-cdk2 complex during the G1 phase of the human cell cycle.
1992,
Pubmed
Koff,
Negative regulation of G1 in mammalian cells: inhibition of cyclin E-dependent kinase by TGF-beta.
1993,
Pubmed
Krek,
Differential phosphorylation of vertebrate p34cdc2 kinase at the G1/S and G2/M transitions of the cell cycle: identification of major phosphorylation sites.
1991,
Pubmed
Krek,
Cell cycle regulation of vertebrate p34cdc2 activity: identification of Thr161 as an essential in vivo phosphorylation site.
1992,
Pubmed
Lanahan,
Growth factor-induced delayed early response genes.
1992,
Pubmed
Lorca,
Dephosphorylation of cdc2 on threonine 161 is required for cdc2 kinase inactivation and normal anaphase.
1992,
Pubmed
,
Xenbase
Luckow,
High level expression of nonfused foreign genes with Autographa californica nuclear polyhedrosis virus expression vectors.
1989,
Pubmed
Marcote,
A three-dimensional model of the Cdc2 protein kinase: localization of cyclin- and Suc1-binding regions and phosphorylation sites.
1993,
Pubmed
Mathur,
Cobalt-ion chelate affinity chromatography for the purification of brain neutral alpha-D-mannosidase and its separation from acid alpha-D-mannosidase.
1984,
Pubmed
Matsushime,
Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle.
1991,
Pubmed
Matsushime,
Identification and properties of an atypical catalytic subunit (p34PSK-J3/cdk4) for mammalian D type G1 cyclins.
1992,
Pubmed
Matsushime,
D-type cyclin-dependent kinase activity in mammalian cells.
1994,
Pubmed
Meyerson,
A family of human cdc2-related protein kinases.
1992,
Pubmed
Meyerson,
Identification of G1 kinase activity for cdk6, a novel cyclin D partner.
1994,
Pubmed
Murray,
Creative blocks: cell-cycle checkpoints and feedback controls.
1992,
Pubmed
Norbury,
Regulatory phosphorylation of the p34cdc2 protein kinase in vertebrates.
1991,
Pubmed
,
Xenbase
Norbury,
Animal cell cycles and their control.
1992,
Pubmed
Ohtsubo,
Cyclin-dependent regulation of G1 in mammalian fibroblasts.
1993,
Pubmed
Pagano,
Regulation of the cell cycle by the cdk2 protein kinase in cultured human fibroblasts.
1993,
Pubmed
Polyak,
p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest.
1994,
Pubmed
Poon,
The cdc2-related protein p40MO15 is the catalytic subunit of a protein kinase that can activate p33cdk2 and p34cdc2.
1993,
Pubmed
,
Xenbase
Quelle,
Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts.
1993,
Pubmed
Resnitzky,
Acceleration of the G1/S phase transition by expression of cyclins D1 and E with an inducible system.
1994,
Pubmed
Rosenblatt,
Human cyclin-dependent kinase 2 is activated during the S and G2 phases of the cell cycle and associates with cyclin A.
1992,
Pubmed
Sherr,
Mammalian G1 cyclins.
1993,
Pubmed
Shuttleworth,
p40MO15, a cdc2-related protein kinase involved in negative regulation of meiotic maturation of Xenopus oocytes.
1990,
Pubmed
,
Xenbase
Solomon,
Role of phosphorylation in p34cdc2 activation: identification of an activating kinase.
1992,
Pubmed
,
Xenbase
Solomon,
CAK, the p34cdc2 activating kinase, contains a protein identical or closely related to p40MO15.
1993,
Pubmed
,
Xenbase
Stanley,
The macrophage colony-stimulating factor, CSF-1.
1985,
Pubmed
Tsai,
Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase.
1991,
Pubmed
,
Xenbase
Tsai,
The cdk2 kinase is required for the G1-to-S transition in mammalian cells.
1993,
Pubmed
Tushinski,
The regulation of mononuclear phagocyte entry into S phase by the colony stimulating factor CSF-1.
1985,
Pubmed
Xiong,
D type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA.
1992,
Pubmed
van den Heuvel,
Distinct roles for cyclin-dependent kinases in cell cycle control.
1993,
Pubmed
