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Cellular interactions of CRKL, and SH2-SH3 adaptor protein

Author:
  • J ten Hoeve
  • V Kaartinen
  • Thoas Fioretos
  • L Haataja
  • J W Voncken
  • N Heisterkamp
  • J Groffen
Publishing year: 1994
Language: English
Pages: 2563-2567
Publication/Series: Cancer Research
Volume: 54
Issue: 10
Document type: Journal article
Publisher: American Association for Cancer Research Inc.

Abstract english

Chronic myelogenous leukemia is characterized by a specific chromosomal translocation, t(9;22), in which the ABL protooncogene and the BCR gene become juxtaposed. The chimeric BCR/ABL gene produces a P210 fusion protein with deregulated tyrosine kinase activity. We have recently isolated a complementary DNA, CRKL, which could code for an adaptor protein consisting of one SH2 and two SH3 domains and lacking any catalytic domain. In the current study, we show that CRKL is highly phosphorylated in the chronic myelogenous leukemia cell line K562 and that it is a substrate for the p210 BCR/ABL and p145 ABL kinases. BCR/ABL and ABL are coimmunoprecipitated with CRKL in vivo, demonstrating that relatively stable complexes are formed. In addition, the nucleotide exchange factor mSOS1 was found to be coimmunoprecipitated with CRKL. These findings establish a putative signal transduction pathway way through which BCR/ABL mediates its oncogenic activity.

Keywords

  • Medical Genetics

Other

Published
  • ISSN: 1538-7445
Thoas Fioretos
E-mail: thoas.fioretos [at] med.lu.se

Principal investigator

Division of Clinical Genetics

+46 46 222 45 95

+46 70 334 33 67

BMC C13

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