Identification and characterization of Batk, a predominantly brain-specific non-receptor protein tyrosine kinase related to Csk.

A novel cDNA, brain-associated tyrosine kinase (Batk), was isolated from a rat hippocampal library and appears to encode a new member of the Csk subfamily of non-receptor protein tyrosine kinases, with 52% overall 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 domain, followed by a tyrosine kinase domain. Analysis of incompletely spliced Batk cDNAs suggests that the genomic structure of Batk is similar to that of Csk with identical exon/intron boundaries. Batk also shows significant homology (86% overall amino acid identity) to the recently described human megakaryocyte-specific Matk. Although Batk is 41 amino acids shorter than Matk, Southern blot analysis suggests that Batk might be a rat homolog of Matk. Batk is predominantly expressed in the brain, with lower expression in the spleen and undetectable expression in other tissues. In situ hybridization and Northern blot analysis show that Batk is widely distributed throughout the adult brain, being primarily expressed in neurons, including those of the hippocampus and cortex. In contrast, embryos appear to have markedly decreased expression levels. Analysis of postnatal day 1 brain suggests that Batk may be upregulated at birth throughout the brain except in the cerebellum. In view of its homology to Csk, a negative regulator of Src family tyrosine kinases, and its generalized expression in the adult brain, we suggest that Batk may function as a brain-specific regulator of kinases involved in the development and maintenance of the nervous system.