Sh3 Adaptor Protein − Cellular Interactions of Crkl, an Sh2 Updated Version Citing Articles E-mail Alerts Cellular Interactions of Crkl, an Sh2-sh3 Adaptor Protein'

Chronic myelogenous leukemia is characterized by a specific chromo somal translocation, t(9;22), in which the ABL protooncogene and the BCR gene become juxtaposed. The chlmenc 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 1362 and that it is a substrate for the p2lO BCR/ABL and p145 ABL kinases. BCR/ABL and ABL are coimmunoprecipitated with CRKL in vivo, dem onstrating 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 path way through which BCR/ABL mediates its oncogenic activity.