G protein

History

Martin Rodbell were awarded the Nobel Prize in Physiology or Medicine in 1994 for their discovery of and research on G proteins.

Function

G proteins are important diabetes and certain forms of cancer, among other pathologies, are thought to arise due to derangement of G protein signaling.

Types of G protein signaling

G protein can refer to two distinct families of proteins. signal transduction.

Heterotrimeric G proteins

Main article: Heterotrimeric G proteins

Heterotrimeric G proteins share a common mode of action, i.e., activation in response to a conformation change in the signal transduction pathway. However, the specific mechanism differs between different types of G proteins.

Common mechanism

  Receptor activated G proteins are bound to the inside surface of the cell membrane. They consist of the G_α and the tightly-associated G_βγ subunits. At the present time, four main families exist for G_α subunits: G_αs, G_αi, G_αq/11, and G_α12/13. These groups differ primarily in effector recognition, but share a similar mechanism of activation.

Activation

When a guanine nucleotide exchange factor (GEF) that exchanges GTP for GDP on the G_α subunit. In the traditional view of heterotrimeric protein activation, this exchange triggers the dissociation of the G_α subunit from the G_βγ dimer and the receptor. However, models that suggest molecular rearrangement, reorganization, and pre-complexing of effector molecules are beginning to be accepted. Both, G_α-GTP and G_βγ, can then activate different signaling cascades (or second messenger pathways) and effector proteins, while the receptor is able to activate the next G protein.

Termination

The G_α subunit will eventually phospholipase C beta, which possesses GAP activity within its C-terminal region. This is an alternate form of regulation for the G_α subunit.

Specific mechanisms

• G_αs stimulates the production of protein kinase A (PKA). PKA can then phosphorylate a myriad of downstream targets.
• G_αi inhibits the production of cAMP from ATP.
• G_αq/11 stimulates membrane-bound diacylglycerol (DAG).
• G_α12/13 are involved in Rho family GTPase signaling (through RhoGEF superfamily) and control cell cytoskeleton remodeling, thus regulating cell migration.
• G_βγ sometimes also have active functions, e.g., coupling to L-type calcium channels.

Small GTPases

Main article: Small GTPases

Small GTPases also bind GTP and GDP and are involved in GTPases.

Lipidation

In order to associate with the inner leaflet of the plasma membrane, many G proteins are covalently modified with lipid extensions, i.e., they are lipidated.

• Heterotrimeric G protein subunits may be myristolated, palmitoylated, or prenylated.
• Small G proteins may be prenylated.

References

• Eric R. Kandel, James H. Schwartz, Thomas M. Jessell (2000). Principles of neural science. New York: McGraw-Hill. ISBN 0-8385-7701-6. 
• Lodish et al. 2000. Molecular Cell Biology 4th ed. W.H. Freeman and Company, New York.
• Voet, Donald and Judith G. Voet. 1995. Biochemistry 2nd ed. John Wilely & Sons, New York.
• Gilman A (1987). "G proteins: transducers of receptor-generated signals.". Annu Rev Biochem 56: 615-49. PMID 3113327.
• Neves S.R., Ram P.T., Iyengar R. (2002). "G Protein Pathways.". Science 296: 1636-9. PMID: 12040175[1].

v • d • e Membrane transport protein

v • d • e Acid anhydride hydrolases: Dynamin (is a GTPase, is not a G protein) - Tubulin