Guanine nucleotide binding proteins (G proteins) are a family of heterotrimeric proteins which couple seven transmembrane domain receptors to intracellular cascades, including neurotransmitter, growth factor, and hormone signaling pathways (for a recent review, see Rosenbaum, Rasmussen, and Kobilka 2009). Heterotrimeric G proteins are composed of three subunits, Gα, Gß, and Gγ (Figure 1); each of the subunits has many different family members. The GNA11 gene encodes the alpha-11 subunit (Gα11). Receptor activation catalyzes the exchange of GDP (guanosine diphosphate) to GTP (guanosine triphosphate) on the Gα subunit, resulting in the dissociation of the Gα subunit from Gßγ. Both Gα and Gßγ can then activate downstream cellular signaling pathways. The signal is terminated when GTP is hydrolyzed to GDP by the intrinsic GTPase activity of the Gα subunit. Oncogenic mutations result in a loss of this intrinsic GTPase activity, resulting in a constitutively active Gα subunit (Kalinec et al. 1992; Landis et al. 1989).
Figure 1. Schematic of heterotrimeric G protein signaling. Activation of a 7 transmembrane G-protein coupled receptor results in exchange of GDP for GTP on the Gα subunit. The GTP bound form of Gα then dissociates from Gßγ. Multiple downstream cellular effector pathways can be activated by G protein signaling.
Suggested Citation: Lovly, C., J. Sosman, W. Pao. 2015. GNA11. My Cancer Genome https://www.padiracinnovation.org/content/disease/melanoma/gna11/?tab=0 (Updated December 4).
Last Updated: December 4, 2015