TY - JOUR
T1 - Regulation of PAK activation and the T cell cytoskeleton by the linker protein SLP-76
AU - Bubeck Wardenburg, Juliane
AU - Pappu, Rajita
AU - Bu, Jia Ying
AU - Mayer, Bruce
AU - Chernoff, Jonathan
AU - Straus, David
AU - Chan, Andrew C.
N1 - Funding Information:
This work is funded in part by a grant from the National Institutes of Health (T32AI01763, T32AR07279, R01CA71516, and R01GM54168). A. C. C. is a Pew Scholar in the Biomedical Sciences and an Assistant Investigator of the Howard Hughes Medical Institute.
PY - 1998/11
Y1 - 1998/11
N2 - 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 effectors 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.
AB - 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 effectors 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.
UR - http://www.scopus.com/inward/record.url?scp=0032211713&partnerID=8YFLogxK
U2 - 10.1016/s1074-7613(00)80658-5
DO - 10.1016/s1074-7613(00)80658-5
M3 - Article
C2 - 9846482
AN - SCOPUS:0032211713
SN - 1074-7613
VL - 9
SP - 607
EP - 616
JO - Immunity
JF - Immunity
IS - 5
ER -