Abstract
Integrin/ligand binding evokes tyrosine phosphorylation of various proteins. We reported previously that a 105 kD protein (pp105) was tyrosine phosphorylated by the engagement of beta 1 integrins in T lymphocytes. We show here that pp105 is a novel p130Cas (Crk-associated substrate)-related protein. Deduced amino acid sequence revealed that pp105 contains conserved motifs with p130Cas, and both pp105 and p130Cas bind to focal adhesion kinase (pp125FAK) and Crk. However, pp105 has a clearly distinct structure from p130Cas, and pp105 is preferentially expressed in lymphocytes, whereas p130Cas is expressed in adherent cells. With these findings, we designate pp105 as Cas-L, lymphocyte-type Cas. Furthermore, we demonstrate that integrin/ligand binding results in the recruitment of Crk, Nck, and SHPTP2 to pp105. These findings further define the roles of pp105/Cas-L and pp125FAK in the integrin-mediated signaling pathways.
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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Amino Acid Sequence
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Animals
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Base Sequence
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Cell Adhesion Molecules / metabolism*
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Cloning, Molecular
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DNA, Complementary / genetics
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Focal Adhesion Kinase 1
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Focal Adhesion Protein-Tyrosine Kinases
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Integrin beta1 / metabolism*
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Lymphocytes / physiology*
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Molecular Sequence Data
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Phosphoproteins / genetics
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Phosphoproteins / immunology
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Phosphoproteins / metabolism*
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Protein Binding
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Protein-Tyrosine Kinases / metabolism*
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Proto-Oncogene Proteins / genetics*
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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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RNA, Messenger / genetics
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Rats
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Recombinant Proteins / metabolism
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Signal Transduction
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Ubiquitin-Protein Ligases*
Substances
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Adaptor Proteins, Signal Transducing
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Cell Adhesion Molecules
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Crk protein, rat
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DNA, Complementary
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Integrin beta1
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NEDD9 protein, human
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Phosphoproteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-crk
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RNA, Messenger
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Recombinant Proteins
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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, rat
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CBL protein, human