Signal transduction by oncoproteins (G proteins)

The concept of signal transduction was discussed in Regulation of Gene Expression 3. A Variety of Mechanisms in Eukaryotes, and the most popular example involves G proteins, so named due to their ability to bind guanine residues. They are heterotrimeric proteins (with three subunits α, β and γ), located in plasma membrane and transduce extracellular signals received by transmembrane receptors to effector proteins in many eukaryotes (e.g., yeast, plants, Dictyostelium and animals). Siince G proteins tranduce signals, they are also described as 'transducers'. The intra-cellular effector molecules can be diverse, including adenyl cyclase, phospholipases and ion channels. Multiple genes encoding α, β and γ subunits of G proteins have been found in several organisms, with greatest sequence diversity discovered among the a subunits.

G proteins are activated, when GTP binds to the αsubunit (by displacing GDP) and causes its dissociation from the β γ dimer (Fig. 45.9). Such an activation is common to a variety of GTP binding proteins. The separated βγ dimer may carry the message from receptor to effector, although in some cases αsubunit may do this job.

Among oncoproteins, G proteins are represented by Ras proteins, which bind GTP and thus resemble αsubunit. While bound to GTP, Ras becomes active and acts upon its target molecule. Following this interaction, GTPase activity of Ras protein hydrolyses GTP molecule to GDP, thus returning itself to inactive condition (Fig. 45.10).