Characterization of the apoptosis-associated tyrosine kinase (AATYK) expressed in the CNS

We isolated three related cDNA clones from a mouse cerebellar library; the type I cDNA was identical to the gene encoding the apoptosis-associated tyr osine kinase (AATYK), whose expression in myeloid precursor cells is increa sed during growth arrest or apoptosis, Low levels of AATYK mRNA expression mere seen in adult mouse brains but not in embryos. In situ hybridization c onfirmed the widespread expression of AATYK mRNA in neurons throughout the adult brain. AATYK possessed tyrosine kinase activity and was autophosphory lated when expressed in 293 cells. AATYK mRNA expression was rapidly induce d in cultured cerebellar granule cells during apoptosis induced by a low co ncentration of KCl (5 mid). Levels of endogenous AATYK protein were increas ed only slightly, but they were accompanied by an increase in molecular wei ght during apoptosis, Results of the tyrosine phosphatase treatments indica ted that the increase in molecular weight was partly caused by tyrosine pho sphorylation, The number of apoptotic granule cells overexpressing mild-typ e AATYK protein was significantly greater than the number of apoptotic gran ule cells overexpressing a mutant AATYK that lacked tyrosine kinase activit y in low concentrations of RCl. These findings suggest that through its tyr osine kinase activity, AATYK is involved in the apoptosis of mature neurons .