The G protein Gα12 stimulates Bruton's tyrosine kinase and a rasGAP through a conserved PH/BM domain

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Abstract
Heterotrimeric guanine-nucleotide-binding proteins (G proteins) are signal transducers that relay messages from many receptors on the cell surface to modulate various cellular processes1,2,3,4. The direct downstream effectors of G proteins consist of the signalling molecules that are activated by their physical interactions with a Gα or Gβγ subunit. Effectors that interact directly with Gα12 G proteins have yet to be identified5,6. Here we show that Gα12 binds directly to, and stimulates the activity of, Bruton's tyrosine kinase (Btk) and a Ras GTPase-activating protein, Gap1m, 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 Gap1m. 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.