P210(BCR ABL) INDUCES FORMATION OF COMPLEXES CONTAINING FOCAL ADHESION PROTEINS AND THE PROTOONCOGENE PRODUCT P120(C-CBL)/

Chronic myelogenous leukemia (CML) is a myeloproliferative disorder ca used by the t(9;22) translocation. This translocation creates a unique tyrosine kinase oncogene, bcr/abl, whose product, p210(BCR/ABL), is l ocalized to the actin cytoskeleton. One of the major tyrosine phosphop roteins in cells transformed by p210(BCR/ABL) is the protooncoprotein p120(c-Cbl). We have previously shown that p210(BCR/ABL) induces forma tion of a multimeric complex of proteins which include p120(c-Cbl), ph osphotidylinositol-3' kinase, and p210(BCR/ABL) itself. Here we show t hat certain focal adhesion proteins are also part of this complex, inc luding paxillin and talin. The sites in paxillin required to bind to p 120(c-Cbl) in this complex have been partially mapped. The interaction of p120(c-Cbl) with paxillin is specific, since other focal adhesion proteins, such as p125(FAK), vinculin, and alpha-actinin, are not in t his complex. The binding of p120(c-Cbl) to the focal adhesion protein paxillin could contribute to the known adhesive defects of CML cells.