Interactions of CBL with BCR-ABL and CRKL in BCR-ABL-transformed myeloid cells

Arun Bhat, Kathryn Kolibaba, Tsukasa Oda, Sayuri Ohno-Jones, Conor Heaney, Brian Druker

Research output: Contribution to journalArticle

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Abstract

The Philadelphia chromosome, detected in virtually all cases of chronic myelogenous leukemia (CML), is formed by a reciprocal translocation between chromosomes 9 and 22 that fuses BCR-encoded sequences upstream of exon 2 of c-ABL. The BCR-ABL fusion creates a gene whose protein product, p210BCR-ABL, has been implicated as the cause of the disease. Although ABL kinase activity has been shown to be required for the transforming abilities of BCR-ABL and numerous substrates of the BCR-ABL tyrosine kinase have been identified, the requirement of most of these substrates for the transforming function of BCR- ABL is unknown. In this study we mapped a direct binding site of the c-CBL proto-oncogene to the SH2 domain of BCR-ABL. This interaction only occurs under conditions where c-CBL is tyrosine-phosphorylated. Despite the direct interaction of c-CBL with the SH2 domain of BCR-ABL, deletion of the SH2 domain of BCR-ABL did not result in an alteration in the complex formation of BCR-ABL and c-CBL, suggesting that another site of direct interaction between c-CBL and BCR-ABL exists or that another protein mediates an indirect interaction of c-CBL and BCR-ABL. Since CRKL, an SH2, SH3 domain-containing adapter protein is known to bind directly to BCR-ABL and also binds to tyrosine-phosphorylated c-CBL, the ability of CRKL to mediate a complex between c-CBL and BCR-ABL was examined.

Original languageEnglish (US)
Pages (from-to)16170-16175
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number26
DOIs
StatePublished - Jun 27 1997

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src Homology Domains
Myeloid Cells
Chromosomes
Tyrosine
Proteins
Electric fuses
Substrates
Protein-Tyrosine Kinases
Exons
Phosphotransferases
Fusion reactions
Chromosomes, Human, Pair 22
Philadelphia Chromosome
Chromosomes, Human, Pair 9
Binding Sites
Proto-Oncogenes
Leukemia, Myelogenous, Chronic, BCR-ABL Positive

ASJC Scopus subject areas

  • Biochemistry

Cite this

Interactions of CBL with BCR-ABL and CRKL in BCR-ABL-transformed myeloid cells. / Bhat, Arun; Kolibaba, Kathryn; Oda, Tsukasa; Ohno-Jones, Sayuri; Heaney, Conor; Druker, Brian.

In: Journal of Biological Chemistry, Vol. 272, No. 26, 27.06.1997, p. 16170-16175.

Research output: Contribution to journalArticle

Bhat, Arun ; Kolibaba, Kathryn ; Oda, Tsukasa ; Ohno-Jones, Sayuri ; Heaney, Conor ; Druker, Brian. / Interactions of CBL with BCR-ABL and CRKL in BCR-ABL-transformed myeloid cells. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 26. pp. 16170-16175.
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