G Protein Signaling: Insights from New Structures

(Heterotrimeric G Protein Cycle)

Updated 24 February 2004: Animation Now Available

Anita M. PreiningerandHeidi E. Hamm*

1Department of Pharmacology, Vanderbilt University Medical Center, Nashville TN 37232-6600, USA.


*Corresponding author. E-mail: heidi.hamm{at}

Animation. Heterotrimeric G protein cycle. The animation shows the basic heterotrimeric G protein cycle and regulation by an RGS (regulator of G protein signaling) protein, a GDI (guanine nucleotide dissociation inhibitor) protein, or a GEF (guanine nucleotide exchange factor). G proteins are comprised of two subunits, {alpha} and an obligate dimer βγ. The basic cycle shows a G protein-coupled receptor (GPCR) activating the G protein by promoting the exchange of guanosine diphosphate (GDP) for guanosine triphosphate (GTP), which allows the {alpha} and βγ subunits to separate and activate downstream targets. The signal is terminated when the {alpha} subunit hydrolyzes GTP and the {alpha} and βγ subunits reassociate. When only the receptor, the G protein, and target effectors are present, intrinsic GTPase activity of the {alpha} subunit governs signal duration. RGS stimulates the GTPase activity of the {alpha} subunit and terminates signaling faster. GDI prevents the dissociation of GDP from the {alpha} subunit and blocks reassociation of the βγ subunit, thus extending βγ signaling. The presence of a GEF would make activation of the {alpha} subunit faster by increasing rate of GDP release, thereby increasing GTP binding to {alpha} in the presence of an activated receptor. The animation allows the user to choose to play the cycle with or without the added regulators and see the effect on the signaling duration. For simplicity, each of the regulators is shown separately, but in cells there may be multiple regulators present at any given time. Thus, the signal strength and duration are the result of the net effect of all interacting partners. Notice that the action is predominantly localized near the plasma membrane and that βγ is tethered to the plasma membrane by a lipid anchor.

Press "Play" to start the basic G protein cycle in the absence of any regulators other than the receptor. Press the RGS symbol to add RGS; press the GDI symbol to add GDI; press the GEF symbol to add GEF.

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Technical Details

Format: Shockwave Flash Objects (swf file)

Size: 90 kb

Requirements: This animation will play with Macromedia Flash 5 (


Citation: A. M. Preininger, H. E. Hamm, G protein signaling: Insights from new structures. Sci. STKE2004, re3 (2004).

© 2004 American Association for the Advancement of Science