Crkl is the major tyrosine-phosphorylated protein in neutrophils from patients with chronic myelogenous leukemia

Tsukasa Oda, Conor Heaney, John R. Hagopian, Keiko Okuda, James D. Griffin, Brian J. Druker

Research output: Contribution to journalArticle

243 Scopus citations

Abstract

The Philadelphia chromosome (Ph1), detected in virtually all cases of chronic myelogenous leukemia (CML), is formed by a reciprocal translocation between chromosome 9 and 22 that fuses Bcr-encoded sequences upstream of exon 2 of c-Abl. This oncogene produces a fusion protein, p210(bcr-abl), in which the Abl tyrosine kinase activity is elevated. Using anti-phosphotyrosine immunoblotting, we have compared the pattern of phosphotyrosine-containing proteins from freshly prepared neutrophils of patients in the stable phase of CML to normal controls. The only consistent difference was the presence of a 39-kDa tyrosine-phosphorylated protein in 18 out of 18 neutrophil samples from CML patients that was not seen in normal controls. This same protein, as assessed by two-dimensional anti-phosphotyrosine immunoblotting, was also present in cell lines expressing p210(bcr-abl), including K562 cells. Using K562 cells as a source of protein, the 39-kDa protein was purified and identified by microsequencing as Crkl, an SH2/SH3 adaptor protein related to the crk oncogene of the avian sarcoma virus, CT10. A direct interaction between Crkl and Abl has also been shown using a yeast two-hybrid screen.

Original languageEnglish (US)
Pages (from-to)22925-22928
Number of pages4
JournalJournal of Biological Chemistry
Volume269
Issue number37
StatePublished - Sep 16 1994

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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