Phospholipids Can Switch the GTPase Substrate Preference of a GTPase-activating Protein

Erzsébet Ligeti, Marie Claire Dagher, Samuel E. Hernandez, Anthony J. Koleske, Jeffrey Settleman

Research output: Article

53 Citations (Scopus)

Abstract

The major cellular inhibitors of the small GTPases of the Ras superfamily are the GTPase-activating proteins (GAPs), which stimulate the intrinsic GTP hydrolyzing activity of GTPases, thereby inactivating them. The catalytic activity of several GAPs is reportedly inhibited or stimulated by various phospholipids and fatty acids in vitro, indicating a likely physiological role for lipids in regulating small GTPases. We find that the p190 RhoGAP, a potent GAP for the Rho and Rac GTPases, is similarly sensitive to phospholipids. Interestingly, however, several of the tested phospholipids were found to effectively inhibit the RhoGAP activity of p190 but stimulate its RacGAP activity. Thus, phospholipids have the ability to "switch" the GTPase substrate preference of a GAP, thereby providing a novel regulatory mechanism for the small GTPases.

Original languageEnglish
Pages (from-to)5055-5058
Number of pages4
JournalJournal of Biological Chemistry
Volume279
Issue number7
DOIs
Publication statusPublished - febr. 13 2004

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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