Activated Drosophila Ras1 is selectively suppressed by isoprenyl transferase inhibitors

Rachele C. Kauffmann, Yimin Qian, Andreas Vogt, Said M. Sebti, Andrew D. Hamilton, Richard W. Carthew

Research output: Contribution to journalArticle

Abstract

Ras CAAX (C = cysteine, A = aliphatic amino acid, and X = any amino acid) peptidomimetic inhibitors of farnesyl protein transferase suppress Ras- dependent cell transformation by preventing farnesylation of the Ras oncoprotein. These compounds are potential anticancer agents for tumors associated with Ras mutations. The peptidomimetic FTI-254 was tested for Ras1-inhibiting activity in whole animals by injection of activated Ras1(val12) Drosophila larvae. FTI-254 decreased the ability of Ras1(val12) to form supernumerary R7 photoreceptor cells in the compound eye of transformed flies. In contrast, it had no effect on the related supernumerary R7 phenotypes of flies transformed with either the activated sevenless receptor tyrosine kinase, Raf kinase, or a chimeric Ras1(val12) protein that is membrane associated through myristylation instead of isoprenylation. Therefore, FTI-254 acts as an isoprenylation inhibitor to selectively inhibit Ras1(val12) signaling activity in a whole-animal model system.

Original languageEnglish (US)
Pages (from-to)10919-10923
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number24
DOIs
StatePublished - Nov 21 1995

ASJC Scopus subject areas

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