The BCR/ABL oncogene alters interaction of the adapter proteins CRKL and CRK with cellular proteins

Leukemia. 1997 Mar;11(3):376-85. doi: 10.1038/sj.leu.2400590.


The Philadelphia chromosome translocation generates a chimeric oncogene, BCR/ABL, which causes chronic myelogenous leukemia (CML). In primary leukemic neutrophils from patients with CML, the major tyrosine phosphorylated protein is CRKL, an SH2-SH3-SH3 adapter protein which has an overall homology of 60% to CRK, the human homologue of the v-crk oncogene. In cell lines transformed by BCR/ABL, CRKL was tyrosine phosphorylated, while CRK was not. We looked for changes in CRK- and CRKL-binding proteins in Ba/F3 hematopoietic cell lines which were transformed by BCR/ABL. Anti-CRK II or anti-CRKL immunoprecipitates were probed by far Western blotting with CRK II- or CRKL-GST fusion proteins to display CRK- and CRKL-coprecipitating proteins. There was a striking qualitative difference in the proteins coprecipitating with CRKL and CRK II. In untransformed cells, three major proteins coprecipitated with CRKL, identified as C3G, SOS and c-ABL. Each of these proteins was found to interact with the CRKL-SH3 domains, but not the SH2 domain. After BCR/ABL transformation, the CRKL SH3-domain binding proteins did not change, with the exception that BCR/ABL now coprecipitated with CRKL. Compared to CRKL, very few proteins coprecipitated with CRK II in untransformed, quiescent cells. After BCR/ABL transformation, both the CRKL- and CRK-SH2 domains bound to a new complex of proteins of approximate molecular weight 105-120 kDa. The major protein in this complex was identified as p120CBL. Thus, in these hematopoietic cell lines, CRKL is involved to a greater extent than CRK II in normal signaling pathways that involve c-ABL, C3G and SOS. In BCR/ABL-transformed cells, CRKL but not CRK II, appears to form complexes which potentially link BCR/ABL, c-ABL, C3G, and SOS to the protooncoprotein, p120CBL.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Antibodies, Monoclonal
  • Antibody Specificity
  • Cell Line, Transformed
  • Fusion Proteins, bcr-abl / genetics*
  • Genes, abl*
  • Hematopoietic Stem Cells / metabolism*
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Membrane Proteins / metabolism
  • Mice
  • Nuclear Proteins / metabolism*
  • Precipitin Tests
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-cbl
  • Proto-Oncogene Proteins c-crk
  • Son of Sevenless Proteins
  • Ubiquitin-Protein Ligases*
  • src Homology Domains / physiology


  • Adaptor Proteins, Signal Transducing
  • Antibodies, Monoclonal
  • CRKL protein
  • Membrane Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-crk
  • Son of Sevenless Proteins
  • Proto-Oncogene Proteins c-cbl
  • Ubiquitin-Protein Ligases
  • Fusion Proteins, bcr-abl
  • CBL protein, human
  • Cbl protein, mouse