title: K562 cell proliferation is modulated by PLCβ1 through a PKCα-mediated pathway.
abstract: Phospholipase C β1 (PLCβ1) is known to play an important role in cell proliferation. Previous studies reported an involvement of PLCβ1 in G 0-G 1/S transition and G 2/M progression in Friend murine erythroleukemia cells (FELC). However, little has been found about its role in human models. Here, we used K562 cell line as human homologous of FELC in order to investigate the possible key regulatory role of PLCβ1 during cell proliferation of this human cell line. Our studies on the effects of the overexpression of both these isoforms showed a specific and positive connection between cyclin D3 and PLCβ1 in K562 cells, which led to a prolonged S phase of the cell cycle and a delay in cell proliferation. In order to shed light on this mechanism, we decided to study the possible involvement of protein kinases C (PKC), known to be direct targets of PLC signaling and important regulators of cell proliferation. Our data showed a peculiar decrease of PKCα levels in cells overexpressing PLCβ1. Moreover, when we silenced PKCα, by RNAi technique, in order to mimic the effects of PLCβ1, we caused the same upregulation of cyclin D3 levels and the same decrease of cell proliferation found in PLCβ1-overexpressing cells. The key features emerging from our studies in K562 cells is that PLCβ1 targets cyclin D3, likely through a PKCα-mediated-pathway, and that, as a downstream effect of its activity, K562 cells undergo an accumulation in the S phase of the cell cycle.
authors: Cellular Signaling Laboratory, Department of Biomedical Sciences, University of Bologna, Bologna, Italy.
authors: Alessandro
authors: A
authors: Poli
authors: Irene
authors: I
authors: Faenza
authors: Francesca
authors: F
authors: Chiarini
authors: Alessandro
authors: A
authors: Matteucci
authors: James A
authors: JA
authors: McCubrey
authors: Lucio
authors: L
authors: Cocco
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D056743:Cyclin D3 / Q000378:metabolism; D006801:Humans; D054799:Phospholipase C beta / Q000235:genetics / Q000378:metabolism*; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D059807:S Phase Cell Cycle Checkpoints; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D056743:Cyclin D3; D034741:RNA, Small Interfering; D051571:Protein Kinase C-alpha; D054799:Phospholipase C beta
keywords: FELC; K562; PKCα; PLCβ1; cell proliferation; cyclin D3; knockdown; overexpression
references: Cancer Res. 2009 Feb 1;69(3):810-8
references: 19155308
references: Oncotarget. 2012 Mar;3(3):224-5
references: 22538871
references: Cell Signal. 2008 Nov;20(11):2013-21
references: 18694821
references: BMB Rep. 2008 Jun 30;41(6):415-34
references: 18593525
references: Cell Cycle. 2011 Jul 15;10(14):2295-8
references: 21715978
references: Front Immunol. 2013 Jan 17;3:423
references: 23335926
references: J Biol Chem. 1996 Aug 30;271(35):21187-92
references: 8702889
references: J Biol Chem. 1993 May 5;268(13):9194-7
references: 8486620
references: Cell Cycle. 2011 Oct 15;10(20):3425
references: 22024932
references: J Biol Chem. 1998 May 8;273(19):11650-9
references: 9565585
references: Am J Physiol Endocrinol Metab. 2010 Mar;298(3):E395-402
references: 19934406
references: J Cell Biochem. 2008 Jan 1;103(1):9-20
references: 17486587
references: J Cell Sci. 2000 Sep;113 ( Pt 17):3025-35
references: 10934041
references: Biochem Pharmacol. 2004 May 15;67(10):1873-86
references: 15130764
references: Biochim Biophys Acta. 1998 Jan 5;1389(1):76-80
references: 9443606
references: J Biol Chem. 1994 Mar 18;269(11):8240-5
references: 7510682
references: Cell Cycle. 2012 Oct 1;11(19):3701-2
references: 22895010
references: Nat Immunol. 2006 Nov;7(11):1157-65
references: 17013388
references: Cell Cycle. 2011 Oct 15;10(20):3430
references: 22024928
references: J Biol Chem. 2001 Aug 31;276(35):32407-10
references: 11432875
references: Cell Cycle. 2012 Jan 1;11(1):57-64
references: 22186781
references: Adv Biol Regul. 2012 Jan;52(1):166-82
references: 22019900
references: Cell Cycle. 2011 Sep 1;10(17):3003-15
references: 21869603
references: J Biol Chem. 1992 Jun 25;267(18):12393-6
references: 1319994
references: Biochem J. 1999 Sep 1;342 ( Pt 2):337-44
references: 10455020
references: Cell Prolif. 2003 Jun;36(3):131-49
references: 12814430
references: J Cell Physiol. 2004 Nov;201(2):259-65
references: 15334660
references: Eur J Biochem. 1997 Aug 15;248(1):1-9
references: 9310352
references: Leukemia. 2011 Feb;25(2):271-80
references: 21109771
references: Int J Cancer. 2009 Dec 1;125(11):2556-64
references: 19672862
references: Adv Enzyme Regul. 2011;51(1):2-12
references: 21035488
references: Oncotarget. 2012 Oct;3(10):1068-111
references: 23085539
references: J Cell Sci. 1992 Mar;101 ( Pt 3):671-9
references: 1522149
references: Arch Biochem Biophys. 2011 May 15;509(2):186-90
references: 21338571
references: Nature. 1992 Jul 16;358(6383):242-5
references: 1321347
references: Adv Biol Regul. 2012 Jan;52(1):2-6
references: 21982979
references: Oncotarget. 2012 Dec;3(12):1505-21
references: 23455493
references: Cell Cycle. 2011 Dec 15;10(24):4195-6
references: 22156915
references: Cell Cycle. 2012 Apr 15;11(8):1583-92
references: 22441823
references: Cell Cycle. 2012 Nov 1;11(21):3913
references: 23032266
references: J Biol Chem. 2000 Sep 29;275(39):30520-4
references: 10913438
references: J Biol Chem. 2001 May 4;276(18):14980-6
references: 11278470
references: FASEB J. 2009 Mar;23(3):957-66
references: 19028838
references: Biochem J. 1998 Jun 1;332 ( Pt 2):281-92
references: 9601053
references: Science. 1992 Oct 23;258(5082):607-14
references: 1411571
references: Leukemia. 2012 Dec;26(12):2474-82
references: 22596089
references: J Lipid Res. 2009 Apr;50 Suppl:S266-71
references: 19033211
references: Biochim Biophys Acta. 2001 Jan 15;1530(1):1-14
references: 11341954
references: Biochem Soc Trans. 1997 May;25(2):571-5
references: 9191158