Conditional requirement for dimerization of the membrane-binding module for BTK signaling in lymphocyte cell lines.

ABSTRACT: Bruton's tyrosine kinase (BTK) is a major drug target in immune cells. The membrane-binding pleckstrin homology and tec homology (PH-TH) domains of BTK are required for signaling. Dimerization of the PH-TH module strongly stimulates the kinase activity of BTK in vitro. Here, we investigated whether BTK dimerizes in cells using the PH-TH module and whether this dimerization is necessary for signaling. To address this question, we developed high-throughput mutagenesis assays for BTK function in Ramos B cells and Jurkat T cells. We measured the fitness costs for thousands of point mutations in the PH-TH module and kinase domain to assess whether dimerization of the PH-TH module and BTK kinase activity were necessary for function. In Ramos cells, we found that neither PH-TH dimerization nor ki

SUBMITTER: Eisen TJ 

PROVIDER: S-EPMC11970436 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature