E41K mutation activates Bruton's tyrosine kinase by stabilizing an inositol hexakisphosphate-dependent invisible dimer.

ABSTRACT: Bruton's tyrosine kinase (BTK) regulates diverse cellular signaling of the innate and adaptive immune system in response to microbial pathogens. Downregulation or constitutive activation of BTK is reported in patients with autoimmune diseases or various B-cell leukemias. BTK is a multidomain protein tyrosine kinase that adopts an Src-like autoinhibited conformation maintained by the interaction between the kinase and PH-TH domains. The PH-TH domain plays a central role in regulating BTK function. BTK is activated by binding to PIP₃ at the plasma membrane upon stimulation by the B-cell receptor (BCR). The PIP₃ binding allows dimerization of the PH-TH domain and subsequent transphosphorylation of the activation loop. Alternatively, a recent study shows that the multival

SUBMITTER: Chowdhury S 

PROVIDER: S-EPMC11338949 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature