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
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Antigen-Presenting Cells / immunology
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Antigen-Presenting Cells / metabolism
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Base Sequence
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Binding Sites
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Cell Cycle Proteins / chemistry
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Cell Cycle Proteins / genetics
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Cell Cycle Proteins / metabolism*
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DNA / genetics
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Guanine Nucleotide Exchange Factors / chemistry
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Guanine Nucleotide Exchange Factors / genetics
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Guanine Nucleotide Exchange Factors / metabolism*
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Humans
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Jurkat Cells
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Multiprotein Complexes
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Phospholipase C gamma
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Phosphoproteins / deficiency
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Phosphoproteins / metabolism*
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Protein Serine-Threonine Kinases / chemistry
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism*
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Proto-Oncogene Proteins / deficiency
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-vav
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Receptors, Antigen, T-Cell / metabolism
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Recombinant Proteins / chemistry
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Rho Guanine Nucleotide Exchange Factors
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Signal Transduction
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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Transcription, Genetic
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Type C Phospholipases / antagonists & inhibitors
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cdc42 GTP-Binding Protein / metabolism
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p21-Activated Kinases
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rac GTP-Binding Proteins / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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Cell Cycle Proteins
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Guanine Nucleotide Exchange Factors
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Multiprotein Complexes
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Phosphoproteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-vav
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Receptors, Antigen, T-Cell
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Recombinant Proteins
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Rho Guanine Nucleotide Exchange Factors
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SLP-76 signal Transducing adaptor proteins
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VAV1 protein, human
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DNA
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PAK1 protein, human
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Protein Serine-Threonine Kinases
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p21-Activated Kinases
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Type C Phospholipases
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Phospholipase C gamma
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cdc42 GTP-Binding Protein
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rac GTP-Binding Proteins