title: CRKL binding to BCR-ABL and BCR-ABL transformation.
abstract: The SH2-SH3 domain-containing adaptor protein CRKL is the predominant tyrosine phosphorylated protein in chronic myelogenous leukemia (CML) neutrophils and BCR-ABL-expressing cell lines. The amino terminal CRKL SH3 domain binds directly to a proline-rich region in the C-terminus of BCR-ABL. BCR-ABL mutants with deletions of this region were constructed to assess biologic effects of eliminating the CRKL binding site. Yeast two-hybrid analysis and gel overlay assays show eradication of the direct interaction of CRKL with BCR-ABL in the proline deletion mutants. However, these BCR-ABL mutants transform myeloid cells to growth factor independence, and in these cells CRKL is tyrosine phosphorylated and associates with BCR-ABL. These findings suggest both direct and indirect interactions of CRKL with BCR-ABL. Thus, disruption of the direct interaction with BCR-ABL has not excluded a role for CRKL in BCR-ABL-mediated transformation.
authors: Division of Hematology and Medical Oncology, Oregon Health Sciences University, Portland 97201, USA.
authors: K S
authors: KS
authors: Kolibaba
authors: A
authors: A
authors: Bhat
authors: C
authors: C
authors: Heaney
authors: T
authors: T
authors: Oda
authors: B J
authors: BJ
authors: Druker
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D001665:Binding Sites / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D016044:Fusion Proteins, bcr-abl / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011392:Proline / Q000235:genetics / Q000502:physiology; D011485:Protein Binding / Q000235:genetics; D017384:Sequence Deletion / Q000235:genetics; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C082869:CRKL protein; D009687:Nuclear Proteins; D014443:Tyrosine; D011392:Proline; D016044:Fusion Proteins, bcr-abl