Nuclear signalling by Rac GTPase: Essential role of phospholipase A2

Byung Chul Kim, Jae Hong Kim

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

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 cotransfection 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.

Original languageEnglish
Pages (from-to)333-337
Number of pages5
JournalBiochemical Journal
Volume326
Issue number2
DOIs
Publication statusPublished - 1997 Sep 1
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this