G proteins: out of the cytoskeletal closet.

This article contains a brief review of GTP-binding proteins (G protein) signaling mechanism with emphasis on accumulated information which suggests that G proteins are multimeric proteins structured such that one receptor can catalytically activate each of the monomers as it moves in an oscillatory fashion along the multimeric chain. Movement is dictated by the binding of GTP or GDP controlled by the exchange reaction induced by agonist binding to the receptor. Based on the dynamic instability model for the interactions of myosin and F-actin, the hypothesis is presented that a GTP-bound monomer is released from one end of the multimer allowing it to interact with effectors such as adenylyl cyclase embedded in the plasma membrane. Association with the enzyme results in a transition, state of the enzyme-G protein complex. In the presence of magnesium, the GTPase on the alpha-subunit of Gs (which stimulates adenylyl cyclase is activated, resulting in the interaction of the alpha- and beta gamma-subunits of Gs with different domains of adenylyl cyclase. In this fashion, the GTPase is not simply a turn off mechanism, but induces a new configuration of the G protein cyclase complex allowing for greatly enhanced cyclic AMP formation. Dissociation of bound Pi may be one of the rate-limiting steps allowing for cycling of G proteins between the multimer receptor complex and adenylyl cyclase.