Regulation of PAK activation and the T cell cytoskeleton by the linker protein SLP-76.
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.
Bubeck Wardenburg
J
J
Center for Immunology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA.
Pappu
R
R
Bu
J Y
JY
Mayer
B
B
Chernoff
J
J
Straus
D
D
Chan
A C
AC
D000199:Actins / Q000096:biosynthesis; D048868:Adaptor Proteins, Signal Transducing; D001426:Bacterial Proteins / Q000378:metabolism; D001427:Bacterial Toxins; D003599:Cytoskeleton / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation; D029968:Escherichia coli Proteins; D020558:GTP Phosphohydrolases / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors; D006801:Humans; D019169:Jurkat Cells / Q000378:metabolism; D008565:Membrane Proteins; D015513:Oncogene Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav; D012234:Rho Factor / Q000378:metabolism; D013601:T-Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D051746:ZAP-70 Protein-Tyrosine Kinase; D054462:p21-Activated Kinases; D018909:src Homology Domains / Q000502:physiology
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D029968:Escherichia coli Proteins; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; C078332:Nck protein; D015513:Oncogene Proteins; D010750:Phosphoproteins; D011506:Proteins; D051567:Proto-Oncogene Proteins c-vav; D012234:Rho Factor; C092947:SLP-76 signal Transducing adaptor proteins; C496618:VAV1 protein, human; C071524:HokC protein, E coli; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; C515903:PAK1 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020558:GTP Phosphohydrolases