CRKL binding to BCR-ABL and BCR-ABL transformation

Kathryn S. Kolibaba, Arun Bhat, Conor Heaney, Tsukasa Oda, Brian J. Druker

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)119-126
Number of pages8
JournalLeukemia and Lymphoma
Volume33
Issue number1-2
DOIs
StatePublished - Jan 1 1999

Keywords

  • BCR-ABL
  • CRKL
  • Src homology domains
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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