The G protein Gα 12 stimulates Bruton's tyrosine kinase and a rasGAP through a conserved PH/BM domain

摘要

Heterotrimeric guanine-nucleotide-binding proteins (G proteins) are signal transducers that relay messages from many receptors on the cell surface to modulate various cellular processes. The direct downstream effectors of G proteins consist of the signalling molecules that are activated by their physical interactions with a Gα or Gβ γ subunit. Effectors that interact directly with Gα12 G proteins have yet to be identified. Here we show that Gα12 binds directly to, and stimulates the activity of, Bruton's tyrosine kinase (Btk) and a Ras GTPase-activating protein, Gap1~m, in vitro and in vivo. Gα12 interacts with a conserved domain, composed of the pleckstrin-homology domain and the adjacent Btk motif, that is present in both Btk and Gap1~m. Our results are, to our knowledge, the first to identify direct effectors for Gα12 and to show that there is a direct link between heterotrimeric and monomeric G proteins.