Stimulation of the catalytic activity of the tyrosine kinase Btk by the adaptor protein Grb2.

ABSTRACT: The Tec-family kinase Btk contains a lipid-binding Pleckstrin homology and Tec homology (PH-TH) module connected by a proline-rich linker to a 'Src module', an SH3-SH2-kinase unit also found in Src-family kinases and Abl. We showed previously that Btk is activated by PH-TH dimerization, which is triggered on membranes by the phosphatidyl inositol phosphate PIP₃, or in solution by inositol hexakisphosphate (IP₆) (Wang et al., 2015, https://doi.org/10.7554/eLife.06074). We now report that the ubiquitous adaptor protein growth-factor-receptor-bound protein 2 (Grb2) binds to and substantially increases the activity of PIP₃-bound Btk on membranes. Using reconstitution on supported-lipid bilayers, we find that Grb2 can be recruited to membrane-bound Btk through i

SUBMITTER: Nocka LM 

PROVIDER: S-EPMC10132808 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature