TYROSINE PHOSPHORYLATION OF MURINE CRKL

The SH2/SH3 adaptor protein Crkl is abnormally phosphorylated on tyros ine by the Bcr/Abl protein in leukemic cells from patients with Philad elphia-chromosome (Ph)positive leukemia. However, the state of tyrosin e-phosphorylation of crkl in normal tissues is unknown. In the current study, we identified mouse crkl by cDNA cloning and examined expressi on levels and tyrosine-phosphorylation of the mouse crkl protein durin g embryogenesis and in adult tissues. Tyrosine-phosphorylation of crkl was prominent during early development, but decreased at later embryo nic stages and in newborn mice. Expression of both crkl and the relate d crk was ubiquitous in the adult. However, crkl differed considerably from crk in relative tissue distribution, and was more abundant in he matopoietic tissues. With exception of the lung, crkl was mostly prese nt in a non-tyrosine phosphorylated form. Consistent with our previous findings in human patients, murine crkl was phosphorylated on tyrosin e in leukemic tissues of BCR/ABL transgenic animals, but was non-tyros ine phosphorylated in normal mouse bone marrow. We conclude that this crkl tyrosine-phosphorylation by Bcr/Abl in hematopoietic cells is cle arly aberrant and is consistently linked to the development of leukemi a. Identification of proteins interacting with tyrosine-phosphorylated crkl in the leukemic cells of BCR/ABL transgenic mice should reveal m embers of signal transduction pathways activated in Ph-positive leukem ia.