THROMBIN RECEPTOR LIGATION AND ACTIVATED RAC UNCAP ACTIN FILAMENT BARBED ENDS THROUGH PHOSPHOINOSITIDE SYNTHESIS IN PERMEABILIZED HUMAN PLATELETS

被引:588
|
作者
HARTWIG, JH
BOKOCH, GM
CARPENTER, CL
JANMEY, PA
TAYLOR, LA
TOKER, A
STOSSEL, TP
机构
[1] Scripps Res Inst, DEPT IMMUNOL & CELL BIOL, LA JOLLA, CA 92037 USA
[2] BETH ISRAEL HOSP, DEPT MED, DIV HEMATOL, SIGNAL TRANSDUCT LAB, BOSTON, MA 02115 USA
关键词
D O I
10.1016/0092-8674(95)90036-5
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
Cells respond to diverse external stimuli by polymerizing cytoplasmic actin, and recent evidence indicates that GTPases can specify where this polymerization takes place, Actin assembly in stimulated blood platelets occurs where sequestered monomers add onto the fast-growing (barbed) ends of actin filaments (F-actin), which are capped in the resting cells, We report that D3 and D4 polyphosphoinositides, PI(4)P, PI(4,5)P-2, PI(3,4)P-2, and PI(3,4,5)P-3, uncap F-actin in resting permeabilized platelets, The thrombin receptor-activating peptide (TRAP), GTP, and GTP gamma S, but not GDP beta S, also uncap F-actin in permeabilized platelets. GDP beta S inhibits TRAP-induced F-actin uncapping, and PI(4,5)P-2 overcomes this inhibition, Constitutively active mutant Rac, but not Rho, activates uncapping of F-actin, PI(4,5)P-2-binding peptides derived from gelsolin inhibit F-actin uncapping by TRAP, Rac, and GTP gamma S. TRAP and Rac induce rapid PI(4,5)P-2 synthesis in permeabilized platelets. The findings establish a signaling pathway for actin assembly involving Rac in which the final message is phosphoinositide-mediated F-actin uncapping.
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页码:643 / 653
页数:11
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