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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.

Pubmed ID: 11157752


  • Ku GM
  • Yablonski D
  • Manser E
  • Lim L
  • Weiss A


The EMBO journal

Publication Data

February 1, 2001

Associated Grants

  • Agency: NCI NIH HHS, Id: CA72531

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