Cellular interactions of CRKL, and SH2-SH3 adaptor protein

Research output: Contribution to journalArticle

Abstract

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.

Details

Authors
  • J ten Hoeve
  • V Kaartinen
  • Thoas Fioretos
  • L Haataja
  • J W Voncken
  • N Heisterkamp
  • J Groffen
External organisations
  • External Organization - Unknown
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
Original languageEnglish
Pages (from-to)2563-2567
JournalCancer Research
Volume54
Issue number10
Publication statusPublished - 1994
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes