p210BCR/ABL induces formation of complexes containing focal adhesion proteins and the protooncogene product p120c-Cbl.
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.
Salgia
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Division of Hematologic Malignacies, Dana-Farber Cancer Institute, Boston, MA 02115.
Sattler
M
M
Pisick
E
E
Li
J L
JL
Griffin
J D
JD
D048868:Adaptor Proteins, Signal Transducing; D001665:Binding Sites; D002448:Cell Adhesion; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics / Q000378:metabolism*; D046911:Macromolecular Substances; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D051419:Paxillin; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D050721:Proto-Oncogene Proteins c-cbl; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016608:Talin / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D044767:Ubiquitin-Protein Ligases
D048868:Adaptor Proteins, Signal Transducing; C082869:CRKL protein; D003598:Cytoskeletal Proteins; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C496061:PXN protein, human; D051419:Paxillin; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D016608:Talin; D050721:Proto-Oncogene Proteins c-cbl; D044767:Ubiquitin-Protein Ligases; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D016044:Fusion Proteins, bcr-abl; C067419:CBL protein, human