Role of Ca2+-independent phospholipase A2 in cell growth and signaling.
Phospholipase A(2) (PLA(2)) are esterases that cleave glycerophospholipids to release fatty acids and lysophospholipids. Several studies demonstrate that PLA(2) regulate growth and signaling in several cell types. However, few of these studies have focused on Ca2+-independent phospholipase A(2) (iPLA(2) or Group VI PLA(2)). This class of PLA(2) was originally suggested to mediate phospholipid remodeling in several cell types including macrophages. As such, it was labeled as a housekeeping protein and thought not to play as significant of roles in cell growth as its older counterparts cytosolic PLA(2) (cPLA(2) or Group IV PLA(2)) and secretory PLA(2) (sPLA(2) or Groups I-III, V and IX-XIV PLA(2)). However, several recent studies demonstrate that iPLA(2) mediate cell growth, and do so by participating in signal transduction pathways that include epidermal growth factor receptors (EGFR), mitogen activated protein kinases (MAPK), mdm2, and even the tumor suppressor protein p53 and the cell cycle regulator p21. The exact mechanism by which iPLA(2) mediates these pathways are not known, but likely involve the generation of lipid signals such as arachidonic acid, lysophosphatidic acid (LPA) and lysophosphocholines (LPC). This review discusses the role of iPLA(2) in cell growth with special emphasis placed on their role in cell signaling. The putative lipid signals involved are also discussed.
Hooks
Shelley B
SB
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, University of Georgia, Athens, GA 30602, USA.
Cummings
Brian S
BS
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D054522:Group VI Phospholipases A2 / Q000737:chemistry / Q000145:classification / Q000502:physiology*; D006801:Humans; D008055:Lipids / Q000737:chemistry / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*
D008055:Lipids; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human
Biochem Soc Trans. 2001 May;29(Pt 2):358-62
11356183
Endothelium. 2005 Jan-Apr;12(1-2):63-72
16036317
Biochem J. 2007 Sep 15;406(3):427-36
17555408
J Biol Chem. 2000 Apr 7;275(14):9937-45
10744668
Prostaglandins Other Lipid Mediat. 2002 Aug;68-69:3-58
12432908
Biochemistry. 2007 Sep 4;46(35):10170-85
17685585
J Biol Chem. 1999 Apr 2;274(14):9607-16
10092647
Am J Physiol Cell Physiol. 2006 May;290(5):C1350-4
16338969
J Biol Chem. 2004 Sep 10;279(37):38194-200
15252026
J Biol Chem. 2004 Sep 24;279(39):40385-91
15252038
J Biol Chem. 2003 Sep 26;278(39):37569-73
12869546
J Biol Chem. 2006 Nov 24;281(47):35709-16
16966332
Biochemistry. 2006 May 23;45(20):6392-406
16700550
Mod Pathol. 2005 Feb;18(2):212-20
15475936
J Biol Chem. 2008 Apr 11;283(15):9852-62
18208815
J Biol Chem. 1997 Nov 14;272(46):29317-21
9361012
J Biol Chem. 2006 Jul 14;281(28):19501-11
16687414
Biochem Biophys Res Commun. 2005 Feb 4;327(1):287-93
15629460
Biochim Biophys Acta. 2005 Jul 15;1735(2):135-50
15979399
J Biol Chem. 1998 May 29;273(22):13870-7
9593733
Nature. 1999 Dec 23-30;402(6764):884-8
10622253
FEBS Lett. 2002 Oct 30;531(1):2-6
12401193
Cell Signal. 2005 Sep;17(9):1052-62
15993747
Curr Drug Deliv. 2005 Oct;2(4):353-62
16305438
Biochemistry. 2003 Dec 2;42(47):13929-40
14636061
Exp Cell Res. 2003 Mar 10;284(1):2-13
12648462
Exp Cell Res. 1995 Jan;216(1):51-64
7813633
Biochem Pharmacol. 2005 Nov 25;70(11):1697-706
16226224
J Biol Chem. 2007 Aug 31;282(35):25278-89
17613534
J Pharmacol Exp Ther. 2004 Mar;308(3):921-8
14634037
Biochim Biophys Acta. 2006 Nov;1761(11):1246-59
16973413
Curr Opin Oncol. 2001 Nov;13(6):506-13
11673692
J Lipid Res. 2008 Jul;49(7):1477-87
18398221
J Biol Chem. 2006 Nov 10;281(45):33982-96
16966336
Biochim Biophys Acta. 1997 Jan 21;1344(2):189-99
9030195
Curr Med Chem Cardiovasc Hematol Agents. 2004 Jul;2(3):209-18
15320787
Biol Pharm Bull. 2004 Aug;27(8):1174-8
15305016
J Cell Sci. 2006 Mar 15;119(Pt 6):1005-15
16492706
J Cell Sci. 2007 Dec 1;120(Pt 23):4134-43
18032786
Am J Physiol. 1997 Apr;272(4 Pt 2):H1972-80
9139985
J Am Soc Nephrol. 2004 Jun;15(6):1441-51
15153555
Cancer Res. 2006 Mar 15;66(6):3006-14
16540649
Gynecol Oncol. 1998 Dec;71(3):364-8
9887232
Free Radic Biol Med. 2006 Feb 1;40(3):376-87
16443152
Exp Cell Res. 2004 Jun 10;296(2):317-26
15149861
J Neurosci. 2008 Feb 27;28(9):2212-20
18305254
Semin Cell Dev Biol. 2004 Oct;15(5):477-89
15271293
Exp Cell Res. 2003 Nov 1;290(2):437-46
14568001
Lipids. 2001 Jul;36(7):689-700
11521967
Am J Pathol. 2008 Apr;172(4):868-81
18349124
J Lipid Mediat Cell Signal. 1996 Sep;14(1-3):15-23
8906540
J Biol Chem. 2005 Jul 22;280(29):26669-79
15908428
Am J Physiol Cell Physiol. 2005 Feb;288(2):C475-82
15643055
Neuroscientist. 2006 Jun;12(3):245-60
16684969
J Biol Chem. 2006 Jan 6;281(1):187-98
16286468
J Biol Chem. 2003 Oct 31;278(44):43831-7
12928445
J Surg Res. 2006 May;132(1):56-61
16289596
J Biol Chem. 1996 Dec 13;271(50):31937-41
8943239
J Biol Chem. 1994 Mar 25;269(12):9227-33
8132660
J Biol Chem. 1996 Mar 22;271(12):6758-65
8636097
J Biol Chem. 2005 Apr 8;280(14):14028-41
15695510
Proc Natl Acad Sci U S A. 1995 Aug 29;92(18):8527-31
7667324
Biochem J. 2002 Jun 15;364(Pt 3):695-702
12049633
J Neurochem. 2000 Oct;75(4):1575-82
10987838
J Biol Chem. 2001 Apr 20;276(16):13198-208
11278673
Biochem Pharmacol. 2001 Apr 1;61(7):811-6
11274966
J Lipid Mediat Cell Signal. 1996 Sep;14(1-3):3-7
8906538
J Lipid Res. 2004 Feb;45(2):205-13
14657205
J Cell Physiol. 2001 Nov;189(2):237-43
11598909
Regul Pept. 2006 Jan 15;133(1-3):105-14
16330112
Biochim Biophys Acta. 1996 Jul 12;1302(1):55-60
8695655
Invest Ophthalmol Vis Sci. 2007 Feb;48(2):636-43
17251460
J Biol Chem. 2004 Nov 19;279(47):48968-75
15364929
J Biol Chem. 1997 Mar 28;272(13):8576-80
9079688
J Neurochem. 2002 Oct;83(2):259-70
12423237
Br J Pharmacol. 2000 Sep;131(2):255-65
10991918
Biochim Biophys Acta. 2005 Sep 15;1736(2):87-93
16137924
Am J Physiol Renal Physiol. 2002 Sep;283(3):F492-8
12167600
Biochem Pharmacol. 2004 Mar 1;67(5):831-40
15104236
J Biol Chem. 1999 May 14;274(20):13915-27
10318801
Biochem Pharmacol. 2007 Oct 1;74(7):949-59
17531957
Cell Signal. 2000 Apr;12(4):205-14
10781927
Int J Dev Neurosci. 2004 May;22(3):131-5
15140466
J Pharmacol Exp Ther. 2000 Sep;294(3):793-9
10945826
J Biol Chem. 2002 Sep 6;277(36):32807-14
12089145
J Pharmacol Exp Ther. 2006 Sep;318(3):1211-9
16763094
J Pharmacol Exp Ther. 2008 Jul;326(1):59-68
18441250