The Ras antagonist S-farnesylthiosalicylic acid induces inhibition of MAPK activation

被引:50
作者
GanaWeisz, ML
Haklai, R
Marciano, D
Egozi, Y
BenBaruch, G
Kloog, Y
机构
[1] ISRAEL INST BIOL RES,IL-70450 NESS ZIONA,ISRAEL
[2] SHEBA MED CTR,DEPT OBSTET & GYNECOL,TEL HASHOMER,ISRAEL
[3] TEL AVIV UNIV,SACKLER SCH MED,IL-69978 TEL AVIV,ISRAEL
基金
以色列科学基金会;
关键词
D O I
10.1006/bbrc.1997.7582
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Inhibition of Ras-dependent signaling and of oncogenic Ras function by farnesyl transferase inhibitors that block Ras membrane anchorage is limited due to alternative prenylation of Res, Here we demonstrate that inhibition of the Ras-dependent Raf-1-MAPK (mitogen activated protein kinase) cascade is achieved by S-farnesylthiosalicylic acid (FTS) which affects Ras membrane association but not Ras farnesylation, FTS interferes with the activation of naf-l and MAPK and inhibits DNA synthesis in Ras-transformed EJ cells at concentrations similar to these at which if: inhibits EJ cell growth (5-25 mu M). FTS also inhibits MAPK activity and DNA synthesis stimulated by serum, EGF or thrombin in serum-starved untransformed Rat-1 cells, demonstrating the generality of its effects on Ras-dependent signaling, The effects of PTS on MAPK activity developed relatively rapidly (within 2-6 h) consistent with Its rapid effect an Ras membrane anchorage. FTS represents a mew class of Ras antagonists that may be useful for the inhibition of various types of oncogenic Res isoforms independently of their prenylation. (C) 1997 Academic Press.
引用
收藏
页码:900 / 904
页数:5
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