A PAK1-PIX-PKL complex is activated by the T-cell receptor independent of Nck, Slp-76 and LAT.

Given the importance of the Rho GTPase family member Rac1 and the Rac1/Cdc42 effector PAK1 in T-cell activation, we investigated the requirements for their activation by the T-cell receptor (TCR). Rac1 and PAK1 activation required the tyrosine kinases ZAP-70 and Syk, but not the cytoplasmic adaptor Slp-76. Surprisingly, PAK1 was ...
activated in the absence of the transmembrane adaptor LAT while Rac1 was not. However, efficient PAK1 activation required its binding sites for Rho GTPases and for PIX, a guanine nucleotide exchange factor for Rho GTPases. The overexpression of ssPIX that either cannot bind PAK1 or lacks GEF function blocked PAK1 activation. These data suggest that a PAK1-PIX complex is recruited to appropriate sites for activation and that PIX is required for Rho family GTPase activation upstream of PAK1. Furthermore, we detected a stable trimolecular complex of PAK1, PIX and the paxillin kinase linker p95PKL. Taken together, these data show that PAK1 contained in this trimolecular complex is activated by a novel LAT- and Slp-76-independent pathway following TCR stimulation.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Carrier Proteins, Cell Cycle Proteins, GTPase-Activating Proteins, Guanine Nucleotide Exchange Factors, Humans, Jurkat Cells, Lymphocyte Activation, Membrane Proteins, Models, Biological, Molecular Sequence Data, Oncogene Proteins, Phosphoproteins, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Receptors, Antigen, T-Cell, Signal Transduction, T-Lymphocytes, Transfection, ZAP-70 Protein-Tyrosine Kinase, p21-Activated Kinases, rac1 GTP-Binding Protein
EMBO J.
Date: Feb. 01, 2001
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