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Rac, one member of Rho family GTPases, stimulates c-fos serum response element (SRE)-luciferase reporter gene in Rat-2 fibroblast cells. By transient transfection analysis, we demonstrated that the activation of phospholipase A2 (PLA2) and the subsequent production of arachidonic acid (AA) are essential for Rac-induced c-fos SRE activation, implying a critical role for PLA2 in the Rac-signalling pathway to the nucleus. Either pretreatment with mepacrine, a specific inhibitor of PLA2, or co-transfection with the expression plasmid of lipocortin-1, a proposed inhibitory protein of PLA2, selectively abolished RacV12-induced SRE activation. Further, we demonstrated that subsequent metabolism of AA, a major product of Rac-activated PLA2, by lipoxygenase (LO) is essential for Rac-induced c-fos SRE activation. In agreement with the role of the PLA2-AA-LO cascade as a potential mediator of Rac signalling to the nucleus, the addition of exogenous AA stimulated c-fos SRE-luciferase activity in an LO-dependent manner. Together, our results demonstrate that 'Rac-activated PLA2 and subsequent AA metabolism by LO' constitute a novel and specific pathway in Rac GTPase-induced c-fos SRE activation.

Titel:	Nuclear signalling by rac GTPase: essential role of phospholipase A2.
Autor/in / Beteiligte Person:	Kim, BC ; Kim, JH
Zeitschrift:	The Biochemical journal, Jg. 326 ( Pt 2) (1997-09-01), S. 333-7
Veröffentlichung:	London, UK : Published by Portland Press on behalf of the Biochemical Society, 1997
Medientyp:	academicJournal
ISSN:	0264-6021 (print)
DOI:	10.1042/bj3260333
Schlagwort:	Animals Annexins genetics Annexins physiology Arachidonic Acid metabolism Arachidonic Acid pharmacology Cells, Cultured DNA-Binding Proteins genetics GTP-Binding Proteins antagonists & inhibitors Gene Expression Regulation Genes, fos Lipoxygenase genetics Lipoxygenase metabolism Luciferases genetics Nuclear Proteins genetics Oligonucleotides, Antisense genetics Phospholipases A metabolism Phospholipases A2 Proto-Oncogene Proteins physiology Rats Regulatory Sequences, Nucleic Acid drug effects Serum Response Factor Transfection ets-Domain Protein Elk-1 rac GTP-Binding Proteins GTP Phosphohydrolases physiology GTP-Binding Proteins physiology Nuclear Proteins physiology Phospholipases A physiology Signal Transduction Transcription Factors
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Biochem J] 1997 Sep 01; Vol. 326 ( Pt 2), pp. 333-7. MeSH Terms: Signal Transduction* ; Transcription Factors* ; GTP Phosphohydrolases / physiology ; GTP-Binding Proteins / physiology ; Nuclear Proteins / physiology ; Phospholipases A / physiology ; Animals ; Annexins / genetics ; Annexins / physiology ; Arachidonic Acid / metabolism ; Arachidonic Acid / pharmacology ; Cells, Cultured ; DNA-Binding Proteins / genetics ; GTP-Binding Proteins / antagonists & inhibitors ; Gene Expression Regulation ; Genes, fos ; Lipoxygenase / genetics ; Lipoxygenase / metabolism ; Luciferases / genetics ; Nuclear Proteins / genetics ; Oligonucleotides, Antisense / genetics ; Phospholipases A / metabolism ; Phospholipases A2 ; Proto-Oncogene Proteins / physiology ; Rats ; Regulatory Sequences, Nucleic Acid / drug effects ; Serum Response Factor ; Transfection ; ets-Domain Protein Elk-1 ; rac GTP-Binding Proteins References: Science. 1995 Sep 1;269(5228):1270-2. (PMID: 7652575) ; Science. 1995 Jul 21;269(5222):403-7. (PMID: 7618106) ; Curr Biol. 1995 Oct 1;5(10):1191-200. (PMID: 8548291) ; Biochem Biophys Res Commun. 1996 Mar 27;220(3):643-7. (PMID: 8607818) ; J Biol Chem. 1996 Apr 5;271(14):7883-6. (PMID: 8626463) ; Biochem Pharmacol. 1996 Jul 26;52(2):351-6. (PMID: 8694860) ; Dev Biol. 1996 Jul 10;177(1):250-64. (PMID: 8660892) ; Biochem Biophys Res Commun. 1997 Mar 6;232(1):223-6. (PMID: 9125136) ; Proc Natl Acad Sci U S A. 1988 Jan;85(2):416-20. (PMID: 3422434) ; J Biol Chem. 1991 Feb 25;266(6):3800-7. (PMID: 1899867) ; Semin Cancer Biol. 1990 Feb;1(1):47-58. (PMID: 2133110) ; Cell. 1992 Apr 17;69(2):295-303. (PMID: 1314702) ; Cell. 1992 Aug 7;70(3):389-99. (PMID: 1643657) ; Cell. 1992 Aug 7;70(3):401-10. (PMID: 1643658) ; Biochem Biophys Res Commun. 1993 Feb 15;190(3):1115-21. (PMID: 8439311) ; Cell. 1993 Aug 13;74(3):565-75. (PMID: 8348619) ; J Biol Chem. 1994 May 13;269(19):13740-3. (PMID: 8188648) ; Annu Rev Cell Biol. 1994;10:31-54. (PMID: 7888179) ; Nature. 1995 Mar 30;374(6521):457-9. (PMID: 7700355) ; Cell. 1995 Apr 7;81(1):53-62. (PMID: 7536630) ; Cell. 1995 Jun 16;81(6):849-56. (PMID: 7781062) ; Cell. 1995 Jun 30;81(7):1137-46. (PMID: 7600581) ; Cell. 1995 Jun 30;81(7):1147-57. (PMID: 7600582) ; Cell. 1995 Jun 30;81(7):1159-70. (PMID: 7600583) ; EMBO J. 1995 Dec 1;14(23):5957-64. (PMID: 8846788) Substance Nomenclature: 0 (Annexins) ; 0 (DNA-Binding Proteins) ; 0 (Elk1 protein, rat) ; 0 (Nuclear Proteins) ; 0 (Oligonucleotides, Antisense) ; 0 (Proto-Oncogene Proteins) ; 0 (Serum Response Factor) ; 0 (Transcription Factors) ; 0 (ets-Domain Protein Elk-1) ; 27YG812J1I (Arachidonic Acid) ; EC 1.13.11.12 (Lipoxygenase) ; EC 1.13.12.- (Luciferases) ; EC 3.1.1.32 (Phospholipases A) ; EC 3.1.1.4 (Phospholipases A2) ; EC 3.6.1.- (GTP Phosphohydrolases) ; EC 3.6.1.- (GTP-Binding Proteins) ; EC 3.6.5.2 (rac GTP-Binding Proteins) Entry Date(s): Date Created: 19970918 Date Completed: 19970929 Latest Revision: 20190501 Update Code: 20231215 PubMed Central ID: PMC1218674

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Nuclear signalling by rac GTPase: essential role of phospholipase A2.