The G protein G alpha12 stimulates Bruton's tyrosine kinase and a rasGAP through a conserved PH/BM domain.
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 G alpha or Gbetagamma subunit. Effectors that interact directly with G alpha12 G proteins have yet to be identified. Here we show that G alpha12 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. G alpha12 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 G alpha12 and to show that there is a direct link between heterotrimeric and monomeric G proteins.
Jiang
Y
Y
Department of Physiology, Cornell University Medical College, New York, New York 10021, USA.
Ma
W
W
Wan
Y
Y
Kozasa
T
T
Hattori
S
S
Huang
X Y
XY
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001665:Binding Sites; D001798:Blood Proteins / Q000737:chemistry; D019556:COS Cells; D002460:Cell Line; D003001:Cloning, Molecular; D004789:Enzyme Activation; D004926:Escherichia coli; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D010750:Phosphoproteins; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D017482:Receptors, Thromboxane / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D020703:ras GTPase-Activating Proteins
D001798:Blood Proteins; D020690:GTPase-Activating Proteins; D010750:Phosphoproteins; D011506:Proteins; C102193:RASA2 protein, human; D017482:Receptors, Thromboxane; D011993:Recombinant Fusion Proteins; C039077:platelet protein P47; D020703:ras GTPase-Activating Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D005982:Glutathione Transferase; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D019204:GTP-Binding Proteins