Dynamic recruitment of PAK1 to the immunological synapse is mediated by PIX independently of SLP-76 and Vav1.
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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Antigen-Presenting Cells, Base Sequence, Binding Sites, Cell Cycle Proteins, DNA, Guanine Nucleotide Exchange Factors, Humans, Jurkat Cells, Multiprotein Complexes, Phospholipase C gamma, Phosphoproteins, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-vav, Receptors, Antigen, T-Cell, Recombinant Proteins, Signal Transduction, T-Lymphocytes, Transcription, Genetic, Type C Phospholipases, cdc42 GTP-Binding Protein, p21-Activated Kinases, rac GTP-Binding Proteins
Adaptor Proteins, Signal Transducing, Antigen-Presenting Cells, Base Sequence, Binding Sites, Cell Cycle Proteins, DNA, Guanine Nucleotide Exchange Factors, Humans, Jurkat Cells, Multiprotein Complexes, Phospholipase C gamma, Phosphoproteins, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-vav, Receptors, Antigen, T-Cell, Recombinant Proteins, Signal Transduction, T-Lymphocytes, Transcription, Genetic, Type C Phospholipases, cdc42 GTP-Binding Protein, p21-Activated Kinases, rac GTP-Binding Proteins
Nat. Immunol.
Date: Jun. 01, 2005
PubMed ID: 15864311
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