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

The EMBO journal | Feb 1, 2001

http://www.ncbi.nlm.nih.gov/pubmed/11157752

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.

Pubmed ID: 11157752 RIS Download

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 | Rho Guanine Nucleotide Exchange Factors | Signal Transduction | T-Lymphocytes | Transfection | ZAP-70 Protein-Tyrosine Kinase | p21-Activated Kinases | rac1 GTP-Binding Protein