IDENTIFICATION AND CHARACTERIZATION OF BATK, A PREDOMINANTLY BRAIN-SPECIFIC NONRECEPTOR PROTEIN-TYROSINE KINASE RELATED TO CSK

A novel cDNA, brain-associated tyrosine kinase (Batk), was isolated fr om a rat hippocampal library and appears to encode a new member of the Csk subfamily of non-receptor protein tyrosine kinases, with 52% over all amino acid identity to rat Csk. Batk resembles kinases of the Src family in that it contains a Src homology 2 (SH2) domain and an SH3 do main, followed by a tyrosine kinase domain. Analysis of incompletely s pliced Batk cDNAs suggests that the genomic structure of Batk is simil ar to that of Csk with identical exon/intron boundaries. Batk also sho ws significant homology (86% overall amino acid identity) to the recen tly described human megakaryocyte-specific Matk. Although Batk is 41 a mino acids shorter than Matk, Southern blot analysis suggests that Bat k might be a rat homolog of Matk. Batk is predominantly expressed in t he brain, with lower expression in the spleen and undetectable express ion in other tissues. In situ hybridization and Northern blot analysis show that Batk is widely distributed throughout the adult brain, bein g primarily expressed in neurons, including those of the hippocampus a nd cortex. In contrast, embryos appear to have markedly decreased expr ession levels. Analysis of postnatal day 1 brain suggests that Batk ma y be upregulated at birth throughout the brain except in the cerebellu m. In view of its homology to Csk, a negative regulator of Src family tyrosine kinases, and its generalized expression in the adult brain, w e suggest that Batk may function as a brain-specific regulator of kina ses involved in the development and maintenance of the nervous system. (C) 1994 Wiley-Liss, Inc.