Switch-like activation of Bruton's tyrosine kinase by membrane-mediated dimerization.

ABSTRACT: The transformation of molecular binding events into cellular decisions is the basis of most biological signal transduction. A fundamental challenge faced by these systems is that reliance on protein-ligand chemical affinities alone generally results in poor sensitivity to ligand concentration, endangering the system to error. Here, we examine the lipid-binding pleckstrin homology and Tec homology (PH-TH) module of Bruton's tyrosine kinase (Btk). Using fluorescence correlation spectroscopy (FCS) and membrane-binding kinetic measurements, we identify a phosphatidylinositol (3-5)-trisphosphate (PIP₃) sensing mechanism that achieves switch-like sensitivity to PIP₃ levels, surpassing the intrinsic affinity discrimination of PIP₃:PH binding. This mechanism employ

SUBMITTER: Chung JK 

PROVIDER: S-EPMC6561188 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature