EXPRESSION OF RECEPTOR PROTEIN-TYROSINE KINASE TIF IS REGULATED DURING LEUKEMIA-CELL DIFFERENTIATION

tif is a recently cloned and characterized cDNA predicting a transmemb rane protein with a putative tyrosine kinase structure in its cytoplas mic domain. By analysis of the purified tif cytoplasmic domain express ed in Escherichia coli, we have demonstrated that tif is an active pro tein tyrosine kinase capable of autophosphorylation on tyrosine residu es and this phosphorylation is inhibited by a tyrosine-specific inhibi tor genistein. Northern blot analyses of various leukemia cell lines h ave revealed that tif mRNA expression is primarily confined to those b earing erythroid and megakaryocytic phenotypes. Megakaryocytic differe ntiation of K562 and HEL cells induced by phorbol 12-myristate 13-acet ate is accompanied by downregulation of tif mRNA expression. In additi on, treatment of K562 and HEL with hexamethylene bis-acetamide, but no t with hemin, decreases the steady-state level of tif mRNA. These comb ined results suggest that the receptor tyrosine kinase tif is involved in hematopoietic development.