CRKL binding to BCR-ABL and BCR-ABL transformation

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

Research output: Contribution to journalArticle

10 Citations (Scopus)

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
StatePublished - 1999

Fingerprint

src Homology Domains
Proline
Tyrosine
Myeloid Cells
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Intercellular Signaling Peptides and Proteins
Neutrophils
Yeasts
Gels
Binding Sites
Cell Line
Proteins

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Kolibaba, K. S., Bhat, A., Heaney, C., Oda, T., & Druker, B. (1999). CRKL binding to BCR-ABL and BCR-ABL transformation. Leukemia and Lymphoma, 33(1-2), 119-126.

CRKL binding to BCR-ABL and BCR-ABL transformation. / Kolibaba, Kathryn S.; Bhat, Arun; Heaney, Conor; Oda, Tsukasa; Druker, Brian.

In: Leukemia and Lymphoma, Vol. 33, No. 1-2, 1999, p. 119-126.

Research output: Contribution to journalArticle

Kolibaba, KS, Bhat, A, Heaney, C, Oda, T & Druker, B 1999, 'CRKL binding to BCR-ABL and BCR-ABL transformation', Leukemia and Lymphoma, vol. 33, no. 1-2, pp. 119-126.
Kolibaba KS, Bhat A, Heaney C, Oda T, Druker B. CRKL binding to BCR-ABL and BCR-ABL transformation. Leukemia and Lymphoma. 1999;33(1-2):119-126.
Kolibaba, Kathryn S. ; Bhat, Arun ; Heaney, Conor ; Oda, Tsukasa ; Druker, Brian. / CRKL binding to BCR-ABL and BCR-ABL transformation. In: Leukemia and Lymphoma. 1999 ; Vol. 33, No. 1-2. pp. 119-126.
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AB - 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.

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