Regulation of PAK activation and the T cell cytoskeleton by the linker protein SLP-76

被引:230
作者
Wardenburg, JB
Pappu, R
Bu, JY
Mayer, B
Chernoff, J
Straus, D
Chan, AC [1 ]
机构
[1] Washington Univ, Sch Med, Ctr Immunol, Div Rheumatol, St Louis, MO 63110 USA
[2] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA
[3] Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA
[4] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA
[5] Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA
[6] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA
[7] Univ Chicago, Dept Internal Med, Div Gastroenterol, Chicago, IL 60637 USA
关键词
D O I
10.1016/S1074-7613(00)80658-5
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Tyrosine phosphorylation of linker proteins enables the T cell antigen receptor (TCR)-associated protein tyrosine kinases to phosphorylate and regulate effector molecules that generate second messengers. We demonstrate here that the SLP-76 linker protein interacts with both nck, an adaptor protein, and Vav, a guanine nucleotide exchange factor for Rho-family GTPases. The assembly of this tri-molecular complex permits the activated Rho-family GTPases to regulate target effecters that interact through nck. In turn, assembly of this complex mediates the enzymatic activation of the p21-activated protein kinase 1 and facilitates actin polymerization. Hence, phosphorylation of linker proteins not only bridges the TCR-associated PTK, ZAP-70, with downstream effector proteins, but also provides a scaffold to integrate distinct signaling complexes to regulate T cell function.
引用
收藏
页码:607 / 616
页数:10
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