Abstract
Chronic myelogenous leukemia (CML) is a myeloproliferative disorder caused by the t(9;22) translocation. This translocation creates a unique tyrosine kinase oncogene, bcr/abl, whose product, p210BCR/ABL, is localized to the actin cytoskeleton. One of the major tyrosine phosphoproteins in cells transformed by p210BCR/ABL is the protooncoprotein p120c-Cbl. We have previously shown that p210BCR/ABL induces formation of a multimeric complex of proteins which include p120c-Cbl, phosphotidylinositol-3' kinase, and p210BCR/ABL itself. Here we show that certain focal adhesion proteins are also part of this complex, including paxillin and talin. The sites in paxillin required to bind to p120c-Cbl in this complex have been partially mapped. The interaction of pl20c-Cbl with paxillin is specific, since other focal adhesion proteins, such as p125FAK, vinculin, and alpha-actinin, are not in this complex. The binding of p120c-Cbl to the focal adhesion protein paxillin could contribute to the known adhesive defects of CML cells.
Publication types
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Research Support, Non-U.S. Gov't
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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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Binding Sites
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Cell Adhesion
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Cytoskeletal Proteins / chemistry
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Cytoskeletal Proteins / metabolism*
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Fusion Proteins, bcr-abl / genetics
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Fusion Proteins, bcr-abl / metabolism*
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Humans
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
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Leukemia, Myelogenous, Chronic, BCR-ABL Positive / metabolism*
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Macromolecular Substances
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Neoplasm Proteins / genetics
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Neoplasm Proteins / metabolism*
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Nuclear Proteins / metabolism
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Paxillin
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Phosphatidylinositol 3-Kinases
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Phosphoproteins / chemistry
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Phosphoproteins / metabolism*
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Phosphorylation
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Phosphotransferases (Alcohol Group Acceptor) / metabolism
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Protein Binding
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Protein Processing, Post-Translational
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-cbl
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Recombinant Fusion Proteins / metabolism
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Talin / metabolism*
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Transfection
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Tumor Cells, Cultured
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Ubiquitin-Protein Ligases*
Substances
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Adaptor Proteins, Signal Transducing
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CRKL protein
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Cytoskeletal Proteins
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Macromolecular Substances
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Neoplasm Proteins
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Nuclear Proteins
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PXN protein, human
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Paxillin
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Phosphoproteins
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Proto-Oncogene Proteins
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Recombinant Fusion Proteins
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Talin
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Proto-Oncogene Proteins c-cbl
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Ubiquitin-Protein Ligases
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Phosphatidylinositol 3-Kinases
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Phosphotransferases (Alcohol Group Acceptor)
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Fusion Proteins, bcr-abl
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CBL protein, human