Abstract
Cas-L (pp105), a Crk-associated substrate (p130(Cas))-related protein, was first identified as a 105-kDa protein that is tyrosine-phosphorylated following beta1 integrin cross-linking in T cells. Cas-L contains possible multiple binding sites for the Src homology (SH) 2 domains of various signaling molecules, and appears to be involved in signal transduction through phosphorylated tyrosine-mediated protein-protein interaction. Since Cas-L is preferentially expressed in lymphocytes, it is conceivable that Cas-L plays an important role in lymphocyte-specific signals. Here, we show the involvement of Cas-L in the T cell receptor (TCR)/CD3 signaling pathway. Cas-L is transiently phosphorylated following CD3 cross-linking, and tyrosine-phosphorylated Cas-L binds to Crk and C3G. Furthermore, a Cas-L mutant that lacks the SH3 domain, the binding site for focal adhesion kinase (FAK), is also tyrosine-phosphorylated upon CD3 cross-linking, but not upon beta1 integrin crosslinking, suggesting that FAK is not involved in CD3-dependent Cas-L phosphorylation. Taken together, the present study indicates a novel signaling pathway mediated by tyrosine-phosphorylated Cas-L upon the TCR/CD3 stimulation.
Publication types
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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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Antibody Specificity
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CD3 Complex / metabolism*
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Cell Adhesion Molecules / metabolism
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Cell Line
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Focal Adhesion Kinase 1
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Focal Adhesion Protein-Tyrosine Kinases
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Guanine Nucleotide Exchange Factors
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Humans
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Immunologic Capping
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Mutation
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Phosphoproteins / genetics
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Phosphoproteins / immunology
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Phosphoproteins / metabolism*
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Phosphorylation
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Protein Binding
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Protein-Tyrosine Kinases / metabolism
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Proteins / metabolism*
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Proto-Oncogene Proteins / immunology
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-cbl
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Proto-Oncogene Proteins c-crk
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Receptors, Antigen, T-Cell / metabolism*
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Signal Transduction
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Tyrosine / metabolism
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Ubiquitin-Protein Ligases*
Substances
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Adaptor Proteins, Signal Transducing
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CD3 Complex
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Cell Adhesion Molecules
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Guanine Nucleotide Exchange Factors
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NEDD9 protein, human
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Phosphoproteins
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Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-crk
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Receptors, Antigen, T-Cell
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Tyrosine
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Proto-Oncogene Proteins c-cbl
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Ubiquitin-Protein Ligases
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Protein-Tyrosine Kinases
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Focal Adhesion Kinase 1
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Focal Adhesion Protein-Tyrosine Kinases
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PTK2 protein, human
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CBL protein, human