BTK autoinhibition analyzed by high-throughput swaps of SH2 domains.

ABSTRACT: Bruton's Tyrosine Kinase (BTK), a Tec-family tyrosine kinase, resembles the Src and Abl kinases in that an SH2-SH3 module regulates the activity of the kinase domain, principally through an inhibitory interaction between the SH3 and kinase domains. In Src-family kinases, phosphorylation of a C-terminal tail latches the SH2 domain onto the kinase domain, stabilizing the inhibitory conformation of the SH3 domain; in Abl, interaction between the kinase domain and a myristoyl group on the N-terminal segment provides a similar latching function. The structure of autoinhibited BTK resembles that of the Src and Abl kinases, but BTK lacks an obvious SH2-kinase latch. To assess the role of the SH2 domain in autoinhibition of BTK, we generated hundreds of chimeric BTK molecules in which the native S

SUBMITTER: Eisen TJ 

PROVIDER: S-EPMC12541323 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature