G protein cycle

Stimulation and inhibition of the enzyme by the GPCR-G-protein cycle occur by analogous mechanisms. Agonists induce hormone receptors to increase a Ga-GDP-GTP exchange and subsequent Ga 3y dissociation (GDP-a py + GTP GTP-ax + [3y + GDP) (Fig. 4). Consequently, agents that affect either the dissociation of either G or Gs, or the association of their respective as, a , or (3y subunits with adenylyl cyclase could affect rates of cAMP formation in enzyme preparations or in intact cells and tissues. There are several important examples. Gas is stably activated by poorly hydrolyzable analogs of GTP, e.g. GTPyS... 

FIGURE 7.4 Diagram of G-protein cycle with (in this case) activation of the effector by the GTP-bound a subunit. See text for letters. (Adapted from Neer and Clapham, Nature, 333, 129, 1988. With permission.)... 

Helms, J. B. Role of heterotrimeric GTP binding proteins in vesicular protein transport indications for both classical and alternative G protein cycles. FEBS Lett. 369 84-88, 1995. 

Figure 12.23 Comparison of the G-protein cycle and the phosphorylase interconversion cycle. The comparison should help to explain the principle underlying the concept of the interconversion cycle and to understand more readilly the G-protein system.

Hess HA, Roper JC, Grill SW, Koelle MR (2004) RGS-7 completes a receptor-independent heterotrimeric G protein cycle to asymmetrically regulate mitotic spindle positioning in C. elegans. Cell 119 209-218 Higashijima T, Burnier J, Ross EM (1990) Regulation of Gi and Go by mastoparan, related amphiphilic peptides, and hydrophobic amines mechanism and structural determinants of activity. J Biol Chem 265 14176-14186... 

Binding of phosducin to the Pycomplex leads to its translocation from the membrane into the cytosol. In this way, the number of Py-complexes available for the G-protein cycle is reduced and signal transmission is weakened. Interestingly, the phosdu-cin function is subject to regulation by phosphorylation. In the Ser-phosphorylated form, binding to the Py-complex is greatly weakened. 

Figure 10.16 G-protein cycle. [Adapted from R. D. Vale, J. Cell Biol. 135,291 (1996).]...

The Adenylate Cyclase Pathway Is Triggered by a Membrane-Bound Receptor The G Protein Cycle Is a Target for Certain Bacterial Toxins... 

The G Protein Cycle Is a Target for Certain Bacterial Toxins... 

Despite the fundamental importance of receptor-catalyzed G protein activation in cellular signaling, relatively little is known about this process as compared to the other regulatory events in the G protein cycle. Crystal structures of inactive rhodopsin and G protein heterotrimers provide the structural context for the meaningful interpretation of the results of the numerous biochemical and biophysical studies described in the preceding sections. Enough data has been accumulated to begin to develop rudimentary models of the receptor-G protein complex that meet some of... 

There is a wealth of biochemical data on the activation of G proteins by receptors. Based on this very large body of evidence coming largely from experiments with cell membranes and reconstituted systems with the purified proteins, the now classical G protein cycle has been proposed (Bourne et at., 1990 Gilman, 1987). The core characteristic of this cycle is that the activated receptor causes GTP binding and subsequent dissociation of the heterotrimeric G protein into the active a. and fly subunits. FRET- and BRET-based assays have recendy been developed in order to investigate G protein activation in intact systems and also to assess whether G protein dissociation is indeed a requirement for G protein activation in the intact cell membrane. 

Fig. 1. G protein cycles. Regulation of both the heterotrimeric G proteins and the monomeric GTPases involves a guanine nucleotide cycle. The active state of the G proteins has bound GTP and is determined by the balance between two major regulatory mechanisms determining guanine nucleotide exchange (activation) and hydrolysis of GTP (inactivation). See text for further details.

Fig. 1 Diagram of G-protein cycle following receptor activation. See text for description. Ag = agonist. (Adapted from Wettschureck Offermanns 2005, Physiol Rev 85 1159-1204, with...

Binding of a- and Py-subunits to phosducin in light-adapted rods blocks the re-formation of the aPy-complex and reduces the turnover of the G-protein cycle. Consequently, phosducin dampens the response to ligjit. In the dark-adapted eye, phosducin is inactive, because it is phosphorylated by the cAMP-dependent protein kinase and perhaps by other kinases. In the light phospho-phosducin is reactivated by dephosphorylation. 

Figure 28-5 The G-protein cycle. (From Conn PM, Meimed S, eds.Texdjook of endocrinoiogy.Towanta NJ Humana Press 1997.)...

Ishii, M., Inanobe, A. and Kurachi, Y. (2002) PIP3 inhibition of RGS protein and its reversal by Ca2+/calmodulin mediate voltage-dependent control of the G protein cycle in a cardiac K+ channel. 

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