Thoas Fioretos
Research team manager
Cellular interactions of CRKL, and SH2-SH3 adaptor protein
Author
Summary, in 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.
Publishing year
1994
Language
English
Pages
2563-2567
Publication/Series
Cancer Research
Volume
54
Issue
10
Links
Document type
Journal article
Publisher
American Association for Cancer Research Inc.
Topic
- Medical Genetics
Status
Published
ISBN/ISSN/Other
- ISSN: 1538-7445