Dynamic recruitment of PAK1 to the immunological synapse is mediated by PIX independently of SLP-76 and Vav1

Nat Immunol. 2005 Jun;6(6):608-17. doi: 10.1038/ni1199. Epub 2005 May 1.

Abstract

T cell receptor engagement activates p21-activated kinase 1 (PAK1) through a LAT-SLP-76-Nck-Vav-Rac-dependent pathway. A second independent pathway involving a GIT-PIX-PAK1 trimolecular complex is also activated by T cell receptor ligation. Here we show a Vav-independent pathway exists that leads to PAK1 activation. In addition, PAK1, PIX and GIT1 were recruited to the T cell-antigen-presenting cell contact site independently of SLP-76 and Vav1. PAK1 recruitment to the T cell-antigen-presenting cell interface required interaction with PIX, which also led to optimal PLC-gamma1 activation and T cell receptor-dependent transcriptional responses. These data indicate that a pathway involving the GIT-PIX-PAK1 complex has a crucial function in PAK1 activation by recruiting PAK1 to the immunological synapse.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • Base Sequence
  • Binding Sites
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • DNA / genetics
  • Guanine Nucleotide Exchange Factors / chemistry
  • Guanine Nucleotide Exchange Factors / genetics
  • Guanine Nucleotide Exchange Factors / metabolism*
  • Humans
  • Jurkat Cells
  • Multiprotein Complexes
  • Phospholipase C gamma
  • Phosphoproteins / deficiency
  • Phosphoproteins / metabolism*
  • Protein-Serine-Threonine Kinases / chemistry
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / deficiency
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-vav
  • Receptors, Antigen, T-Cell / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Rho Guanine Nucleotide Exchange Factors
  • Signal Transduction
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism
  • Transcription, Genetic
  • Type C Phospholipases / antagonists & inhibitors
  • cdc42 GTP-Binding Protein / metabolism
  • p21-Activated Kinases
  • rac GTP-Binding Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Cycle Proteins
  • Guanine Nucleotide Exchange Factors
  • Multiprotein Complexes
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-vav
  • Receptors, Antigen, T-Cell
  • Recombinant Proteins
  • Rho Guanine Nucleotide Exchange Factors
  • SLP-76 signal Transducing adaptor proteins
  • VAV1 protein, human
  • DNA
  • PAK1 protein, human
  • Protein-Serine-Threonine Kinases
  • p21-Activated Kinases
  • Type C Phospholipases
  • Phospholipase C gamma
  • cdc42 GTP-Binding Protein
  • rac GTP-Binding Proteins