Identification of G1 kinase activity for cdk6, a novel cyclin D partner. (original) (raw)
- Journal List
- Mol Cell Biol
- v.14(3); 1994 Mar
- PMC358568
Mol Cell Biol. 1994 Mar; 14(3): 2077–2086.
Massachusetts General Hospital Cancer Center, Charlestown 02129.
Abstract
A family of vertebrate cdc2-related kinases has been identified, and these kinases are candidates for roles in cell cycle regulation. Here, we show that the human PLSTIRE gene product is a novel cyclin-dependent kinase, cdk6. The cdk6 kinase is associated with cyclins D1, D2, and D3 in lysates of human cells and is activated by coexpression with D-type cyclins in Sf9 insect cells. Furthermore, we demonstrate that endogenous cdk6 from human cell extracts is an active kinase which can phosphorylate pRB, the product of the retinoblastoma tumor suppressor gene. The activation of cdk6 kinase occurs during mid-G1 in phytohemagglutinin-stimulated T cells, well prior to the activation of cdk2 kinase. This timing suggests that cdk6, and by analogy its homolog cdk4, links growth factor stimulation with the onset of cell cycle progression.
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- Ajchenbaum F, Ando K, DeCaprio JA, Griffin JD. Independent regulation of human D-type cyclin gene expression during G1 phase in primary human T lymphocytes. J Biol Chem. 1993 Feb 25;268(6):4113–4119. [PubMed] [Google Scholar]
- Akiyama T, Ohuchi T, Sumida S, Matsumoto K, Toyoshima K. Phosphorylation of the retinoblastoma protein by cdk2. Proc Natl Acad Sci U S A. 1992 Sep 1;89(17):7900–7904. [PMC free article] [PubMed] [Google Scholar]
- Ando K, Ajchenbaum-Cymbalista F, Griffin JD. Regulation of G1/S transition by cyclins D2 and D3 in hematopoietic cells. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9571–9575. [PMC free article] [PubMed] [Google Scholar]
- Baldin V, Lukas J, Marcote MJ, Pagano M, Draetta G. Cyclin D1 is a nuclear protein required for cell cycle progression in G1. Genes Dev. 1993 May;7(5):812–821. [PubMed] [Google Scholar]
- Bates S, Bonetta L, MacAllan D, Parry D, Holder A, Dickson C, Peters G. CDK6 (PLSTIRE) and CDK4 (PSK-J3) are a distinct subset of the cyclin-dependent kinases that associate with cyclin D1. Oncogene. 1994 Jan;9(1):71–79. [PubMed] [Google Scholar]
- Buchkovich K, Duffy LA, Harlow E. The retinoblastoma protein is phosphorylated during specific phases of the cell cycle. Cell. 1989 Sep 22;58(6):1097–1105. [PubMed] [Google Scholar]
- Bunnell BA, Heath LS, Adams DE, Lahti JM, Kidd VJ. Increased expression of a 58-kDa protein kinase leads to changes in the CHO cell cycle. Proc Natl Acad Sci U S A. 1990 Oct;87(19):7467–7471. [PMC free article] [PubMed] [Google Scholar]
- Chellappan SP, Hiebert S, Mudryj M, Horowitz JM, Nevins JR. The E2F transcription factor is a cellular target for the RB protein. Cell. 1991 Jun 14;65(6):1053–1061. [PubMed] [Google Scholar]
- Chen PL, Scully P, Shew JY, Wang JY, Lee WH. Phosphorylation of the retinoblastoma gene product is modulated during the cell cycle and cellular differentiation. Cell. 1989 Sep 22;58(6):1193–1198. [PubMed] [Google Scholar]
- Cleveland DW, Fischer SG, Kirschner MW, Laemmli UK. Peptide mapping by limited proteolysis in sodium dodecyl sulfate and analysis by gel electrophoresis. J Biol Chem. 1977 Feb 10;252(3):1102–1106. [PubMed] [Google Scholar]
- DeCaprio JA, Furukawa Y, Ajchenbaum F, Griffin JD, Livingston DM. The retinoblastoma-susceptibility gene product becomes phosphorylated in multiple stages during cell cycle entry and progression. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1795–1798. [PMC free article] [PubMed] [Google Scholar]
- DeCaprio JA, Ludlow JW, Lynch D, Furukawa Y, Griffin J, Piwnica-Worms H, Huang CM, Livingston DM. The product of the retinoblastoma susceptibility gene has properties of a cell cycle regulatory element. Cell. 1989 Sep 22;58(6):1085–1095. [PubMed] [Google Scholar]
- Dowdy SF, Hinds PW, Louie K, Reed SI, Arnold A, Weinberg RA. Physical interaction of the retinoblastoma protein with human D cyclins. Cell. 1993 May 7;73(3):499–511. [PubMed] [Google Scholar]
- Draetta G, Beach D. Activation of cdc2 protein kinase during mitosis in human cells: cell cycle-dependent phosphorylation and subunit rearrangement. Cell. 1988 Jul 1;54(1):17–26. [PubMed] [Google Scholar]
- Elledge SJ, Spottswood MR. A new human p34 protein kinase, CDK2, identified by complementation of a cdc28 mutation in Saccharomyces cerevisiae, is a homolog of Xenopus Eg1. EMBO J. 1991 Sep;10(9):2653–2659. [PMC free article] [PubMed] [Google Scholar]
- Ewen ME, Sluss HK, Sherr CJ, Matsushime H, Kato J, Livingston DM. Functional interactions of the retinoblastoma protein with mammalian D-type cyclins. Cell. 1993 May 7;73(3):487–497. [PubMed] [Google Scholar]
- Ewen ME, Sluss HK, Whitehouse LL, Livingston DM. TGF beta inhibition of Cdk4 synthesis is linked to cell cycle arrest. Cell. 1993 Sep 24;74(6):1009–1020. [PubMed] [Google Scholar]
- Fang F, Newport JW. Evidence that the G1-S and G2-M transitions are controlled by different cdc2 proteins in higher eukaryotes. Cell. 1991 Aug 23;66(4):731–742. [PubMed] [Google Scholar]
- Furukawa Y, Piwnica-Worms H, Ernst TJ, Kanakura Y, Griffin JD. cdc2 gene expression at the G1 to S transition in human T lymphocytes. Science. 1990 Nov 9;250(4982):805–808. [PubMed] [Google Scholar]
- Hanks SK. Homology probing: identification of cDNA clones encoding members of the protein-serine kinase family. Proc Natl Acad Sci U S A. 1987 Jan;84(2):388–392. [PMC free article] [PubMed] [Google Scholar]
- Harlow E, Franza BR, Jr, Schley C. Monoclonal antibodies specific for adenovirus early region 1A proteins: extensive heterogeneity in early region 1A products. J Virol. 1985 Sep;55(3):533–546. [PMC free article] [PubMed] [Google Scholar]
- Helin K, Lees JA, Vidal M, Dyson N, Harlow E, Fattaey A. A cDNA encoding a pRB-binding protein with properties of the transcription factor E2F. Cell. 1992 Jul 24;70(2):337–350. [PubMed] [Google Scholar]
- Hellmich MR, Pant HC, Wada E, Battey JF. Neuronal cdc2-like kinase: a cdc2-related protein kinase with predominantly neuronal expression. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10867–10871. [PMC free article] [PubMed] [Google Scholar]
- Hinds PW, Mittnacht S, Dulic V, Arnold A, Reed SI, Weinberg RA. Regulation of retinoblastoma protein functions by ectopic expression of human cyclins. Cell. 1992 Sep 18;70(6):993–1006. [PubMed] [Google Scholar]
- Hu QJ, Lees JA, Buchkovich KJ, Harlow E. The retinoblastoma protein physically associates with the human cdc2 kinase. Mol Cell Biol. 1992 Mar;12(3):971–980. [PMC free article] [PubMed] [Google Scholar]
- Kaelin WG, Jr, Pallas DC, DeCaprio JA, Kaye FJ, Livingston DM. Identification of cellular proteins that can interact specifically with the T/E1A-binding region of the retinoblastoma gene product. Cell. 1991 Feb 8;64(3):521–532. [PubMed] [Google Scholar]
- Kato J, Matsushime H, Hiebert SW, Ewen ME, Sherr CJ. Direct binding of cyclin D to the retinoblastoma gene product (pRb) and pRb phosphorylation by the cyclin D-dependent kinase CDK4. Genes Dev. 1993 Mar;7(3):331–342. [PubMed] [Google Scholar]
- Kato JY, Sherr CJ. Inhibition of granulocyte differentiation by G1 cyclins D2 and D3 but not D1. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11513–11517. [PMC free article] [PubMed] [Google Scholar]
- Kiyokawa H, Busquets X, Powell CT, Ngo L, Rifkind RA, Marks PA. Cloning of a D-type cyclin from murine erythroleukemia cells. Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2444–2447. [PMC free article] [PubMed] [Google Scholar]
- Koff A, Cross F, Fisher A, Schumacher J, Leguellec K, Philippe M, Roberts JM. Human cyclin E, a new cyclin that interacts with two members of the CDC2 gene family. Cell. 1991 Sep 20;66(6):1217–1228. [PubMed] [Google Scholar]
- Lapidot-Lifson Y, Patinkin D, Prody CA, Ehrlich G, Seidman S, Ben-Aziz R, Benseler F, Eckstein F, Zakut H, Soreq H. Cloning and antisense oligodeoxynucleotide inhibition of a human homolog of cdc2 required in hematopoiesis. Proc Natl Acad Sci U S A. 1992 Jan 15;89(2):579–583. [PMC free article] [PubMed] [Google Scholar]
- Lee MG, Nurse P. Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature. 1987 May 7;327(6117):31–35. [PubMed] [Google Scholar]
- Lees JA, Buchkovich KJ, Marshak DR, Anderson CW, Harlow E. The retinoblastoma protein is phosphorylated on multiple sites by human cdc2. EMBO J. 1991 Dec;10(13):4279–4290. [PMC free article] [PubMed] [Google Scholar]
- Lew DJ, Dulić V, Reed SI. Isolation of three novel human cyclins by rescue of G1 cyclin (Cln) function in yeast. Cell. 1991 Sep 20;66(6):1197–1206. [PubMed] [Google Scholar]
- Lew J, Winkfein RJ, Paudel HK, Wang JH. Brain proline-directed protein kinase is a neurofilament kinase which displays high sequence homology to p34cdc2. J Biol Chem. 1992 Dec 25;267(36):25922–25926. [PubMed] [Google Scholar]
- Lin BT, Gruenwald S, Morla AO, Lee WH, Wang JY. Retinoblastoma cancer suppressor gene product is a substrate of the cell cycle regulator cdc2 kinase. EMBO J. 1991 Apr;10(4):857–864. [PMC free article] [PubMed] [Google Scholar]
- Ludlow JW, DeCaprio JA, Huang CM, Lee WH, Paucha E, Livingston DM. SV40 large T antigen binds preferentially to an underphosphorylated member of the retinoblastoma susceptibility gene product family. Cell. 1989 Jan 13;56(1):57–65. [PubMed] [Google Scholar]
- Matsushime H, Ewen ME, Strom DK, Kato JY, Hanks SK, Roussel MF, Sherr CJ. Identification and properties of an atypical catalytic subunit (p34PSK-J3/cdk4) for mammalian D type G1 cyclins. Cell. 1992 Oct 16;71(2):323–334. [PubMed] [Google Scholar]
- Matsushime H, Quelle DE, Shurtleff SA, Shibuya M, Sherr CJ, Kato JY. D-type cyclin-dependent kinase activity in mammalian cells. Mol Cell Biol. 1994 Mar;14(3):2066–2076. [PMC free article] [PubMed] [Google Scholar]
- Matsushime H, Roussel MF, Ashmun RA, Sherr CJ. Colony-stimulating factor 1 regulates novel cyclins during the G1 phase of the cell cycle. Cell. 1991 May 17;65(4):701–713. [PubMed] [Google Scholar]
- Meyerson M, Enders GH, Wu CL, Su LK, Gorka C, Nelson C, Harlow E, Tsai LH. A family of human cdc2-related protein kinases. EMBO J. 1992 Aug;11(8):2909–2917. [PMC free article] [PubMed] [Google Scholar]
- Meyerson M, Faha B, Su LK, Harlow E, Tsai LH. The cyclin-dependent kinase family. Cold Spring Harb Symp Quant Biol. 1991;56:177–186. [PubMed] [Google Scholar]
- Mihara K, Cao XR, Yen A, Chandler S, Driscoll B, Murphree AL, T'Ang A, Fung YK. Cell cycle-dependent regulation of phosphorylation of the human retinoblastoma gene product. Science. 1989 Dec 8;246(4935):1300–1303. [PubMed] [Google Scholar]
- Motokura T, Bloom T, Kim HG, Jüppner H, Ruderman JV, Kronenberg HM, Arnold A. A novel cyclin encoded by a bcl1-linked candidate oncogene. Nature. 1991 Apr 11;350(6318):512–515. [PubMed] [Google Scholar]
- Motokura T, Keyomarsi K, Kronenberg HM, Arnold A. Cloning and characterization of human cyclin D3, a cDNA closely related in sequence to the PRAD1/cyclin D1 proto-oncogene. J Biol Chem. 1992 Oct 5;267(28):20412–20415. [PubMed] [Google Scholar]
- Ninomiya-Tsuji J, Nomoto S, Yasuda H, Reed SI, Matsumoto K. Cloning of a human cDNA encoding a CDC2-related kinase by complementation of a budding yeast cdc28 mutation. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):9006–9010. [PMC free article] [PubMed] [Google Scholar]
- Nurse P. Universal control mechanism regulating onset of M-phase. Nature. 1990 Apr 5;344(6266):503–508. [PubMed] [Google Scholar]
- Okuda T, Cleveland JL, Downing JR. PCTAIRE-1 and PCTAIRE-3, two members of a novel cdc2/CDC28-related protein kinase gene family. Oncogene. 1992 Nov;7(11):2249–2258. [PubMed] [Google Scholar]
- Pagano M, Draetta G, Jansen-Dürr P. Association of cdk2 kinase with the transcription factor E2F during S phase. Science. 1992 Feb 28;255(5048):1144–1147. [PubMed] [Google Scholar]
- Pagano M, Pepperkok R, Lukas J, Baldin V, Ansorge W, Bartek J, Draetta G. Regulation of the cell cycle by the cdk2 protein kinase in cultured human fibroblasts. J Cell Biol. 1993 Apr;121(1):101–111. [PMC free article] [PubMed] [Google Scholar]
- Palmero I, Holder A, Sinclair AJ, Dickson C, Peters G. Cyclins D1 and D2 are differentially expressed in human B-lymphoid cell lines. Oncogene. 1993 Apr;8(4):1049–1054. [PubMed] [Google Scholar]
- Paris J, Le Guellec R, Couturier A, Le Guellec K, Omilli F, Camonis J, MacNeill S, Philippe M. Cloning by differential screening of a Xenopus cDNA coding for a protein highly homologous to cdc2. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):1039–1043. [PMC free article] [PubMed] [Google Scholar]
- Pines J, Hunter T. p34cdc2: the S and M kinase? New Biol. 1990 May;2(5):389–401. [PubMed] [Google Scholar]
- Quelle DE, Ashmun RA, Shurtleff SA, Kato JY, Bar-Sagi D, Roussel MF, Sherr CJ. Overexpression of mouse D-type cyclins accelerates G1 phase in rodent fibroblasts. Genes Dev. 1993 Aug;7(8):1559–1571. [PubMed] [Google Scholar]
- Riabowol K, Draetta G, Brizuela L, Vandre D, Beach D. The cdc2 kinase is a nuclear protein that is essential for mitosis in mammalian cells. Cell. 1989 May 5;57(3):393–401. [PubMed] [Google Scholar]
- Rosenblatt J, Gu Y, Morgan DO. Human cyclin-dependent kinase 2 is activated during the S and G2 phases of the cell cycle and associates with cyclin A. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2824–2828. [PMC free article] [PubMed] [Google Scholar]
- Sherr CJ. Mammalian G1 cyclins. Cell. 1993 Jun 18;73(6):1059–1065. [PubMed] [Google Scholar]
- Shuttleworth J, Godfrey R, Colman A. p40MO15, a cdc2-related protein kinase involved in negative regulation of meiotic maturation of Xenopus oocytes. EMBO J. 1990 Oct;9(10):3233–3240. [PMC free article] [PubMed] [Google Scholar]
- Solomon MJ, Glotzer M, Lee TH, Philippe M, Kirschner MW. Cyclin activation of p34cdc2. Cell. 1990 Nov 30;63(5):1013–1024. [PubMed] [Google Scholar]
- Taya Y, Yasuda H, Kamijo M, Nakaya K, Nakamura Y, Ohba Y, Nishimura S. In vitro phosphorylation of the tumor suppressor gene RB protein by mitosis-specific histone H1 kinase. Biochem Biophys Res Commun. 1989 Oct 16;164(1):580–586. [PubMed] [Google Scholar]
- Th'ng JP, Wright PS, Hamaguchi J, Lee MG, Norbury CJ, Nurse P, Bradbury EM. The FT210 cell line is a mouse G2 phase mutant with a temperature-sensitive CDC2 gene product. Cell. 1990 Oct 19;63(2):313–324. [PubMed] [Google Scholar]
- Tsai LH, Harlow E, Meyerson M. Isolation of the human cdk2 gene that encodes the cyclin A- and adenovirus E1A-associated p33 kinase. Nature. 1991 Sep 12;353(6340):174–177. [PubMed] [Google Scholar]
- Tsai LH, Lees E, Faha B, Harlow E, Riabowol K. The cdk2 kinase is required for the G1-to-S transition in mammalian cells. Oncogene. 1993 Jun;8(6):1593–1602. [PubMed] [Google Scholar]
- Tsai LH, Takahashi T, Caviness VS, Jr, Harlow E. Activity and expression pattern of cyclin-dependent kinase 5 in the embryonic mouse nervous system. Development. 1993 Dec;119(4):1029–1040. [PubMed] [Google Scholar]
- van den Heuvel S, Harlow E. Distinct roles for cyclin-dependent kinases in cell cycle control. Science. 1993 Dec 24;262(5142):2050–2054. [PubMed] [Google Scholar]
- Won KA, Xiong Y, Beach D, Gilman MZ. Growth-regulated expression of D-type cyclin genes in human diploid fibroblasts. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9910–9914. [PMC free article] [PubMed] [Google Scholar]
- Xiong Y, Connolly T, Futcher B, Beach D. Human D-type cyclin. Cell. 1991 May 17;65(4):691–699. [PubMed] [Google Scholar]
- Xiong Y, Zhang H, Beach D. D type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA. Cell. 1992 Oct 30;71(3):505–514. [PubMed] [Google Scholar]
- Xiong Y, Zhang H, Beach D. Subunit rearrangement of the cyclin-dependent kinases is associated with cellular transformation. Genes Dev. 1993 Aug;7(8):1572–1583. [PubMed] [Google Scholar]
- Zhang H, Xiong Y, Beach D. Proliferating cell nuclear antigen and p21 are components of multiple cell cycle kinase complexes. Mol Biol Cell. 1993 Sep;4(9):897–906. [PMC free article] [PubMed] [Google Scholar]
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