GTP-binding protein-coupled receptors

Bhattacharya, M., Babwah, A. V., and Ferguson, S. S. (2004). Small GTP-binding protein-coupled receptors. Biochem. Soc. Trans. 32, 1040-1044. 

Palczewski, K. GTP-binding-protein-coupled receptor kinases-Two mechanistic models. Eur. J. Biochem., 1997, 248, 261-269. 

A. Noma (1986). GTP-binding proteins couple cardiac muscarinic receptors to potassinm channels. Trends Neurol. Sci. 10 142-143. 

Nucleotide sequences for three distinct pertussis toxin-sensitive hetero-trimeric GTP binding protein-coupled opioid receptors have been reported with —65% homology existing between their amino acids [8-13], These distinct opioid receptors, termed mu, delta, and kappa, have been shown to elicit a variety of pharmacologic actions the most notable is analgesia [5,7],... 

Role of GTP-binding proteins in receptor-response coupling... 

The G-protein-coupled heptahelical receptors are the largest transmembrane receptor class. They may take up 2% of the genome. Altogether, there may be thousands of different receptor molecules of this type that all transmit their signals through a heterotrimeric GTP-binding protein. These receptors are dealt with in Chapter 5. 

As cAMP receptors are members of the GTP-binding protein coupled class of receptors, they exhibit highest affinity for cAMP when complexed with GaPy. Upon cAMP binding, the heterot-rimeric G proteins become uncoupled and the receptors exhibit an affinity decrease. Methods are presented that measure the impact of GTP-binding on cAMP-receptor interaction (14-16). 

G-Protein Coupling. The heterotrimeric guanosine triphosphate (GTP) binding proteins, known as G-proteins, are a principal family of proteins serving to couple membrane receptors of the G-protein family to ionic and biochemical processes. This topic is reviewed in References 63—67. 

Costa, T., and Herz, A. (1989). Antagonists with negative intrinsic activity at 6-opioid receptors coupled to GTP-binding proteins. Proc. Natl. Acad. Sci. U.S.A. 86 7321-7325. 

S-acylated proteins include many GTP-binding regulatory proteins (G proteins), including most a subunits of heterotrimeric G-proteins and also many members of the Ras superfamily of monomeric G proteins, a number of G protein-coupled receptors, several nonreceptor tyrosine kinases, and a number of other signaling molecules, -acylation is posttranslational and reversible, a property that allows the cell to control... 

The H2 receptor is the second class of HA receptors. This is another G-protein-coupled receptor but, unlike the Hi receptor, the H2 receptor is coupled to adenylyl cyclase via the GTP-binding Gs protein (Hill et ah, 1997). Encoded by an intronless gene and located on human chromosome 5, the H2 receptor is made up of c. 358 amino acids (Gantz et ah, 1991 Traiffort et ah, 1995). Activation of the H2 receptor causes an accumulation of cAMP and activation of protein kinase A that eventually leads to the activation of cyclic-AMP-response element (CRE)-binding protein (CREB) (Hill et ah, 1997). In neurons, the H2 receptor mediates its excitatory effects by blocking the Ca2+-dependent K+ channel (Haas Konnerth, 1983). 

Leukotriene B4 has been implicated in inflammatory processes and chemo-taxis. The G-protein-coupled receptor in human myeloid cells was postulated to possess two distinct binding sites. Photoaffinity studies using unmodified tritiated LTB4 as photoreactive species labeled two different proteins in the presence (53 kDa) and in the absence of a non-cleavable GTP analogue (56 kDa). This means that stabilization of the G-protein in the GTP-bound state resulted in an interconversion of the first high affinity binding site to an alternative low-affinity binding site [99]. 

Sekiguchi, M Sakuta, H Okamoto, K., and Sakai, Y. (1990) GABAb receptors expressed in Xenopus oocytes by guinea pig cerebral mRNA are functionally coupled with Ca2+-dependent Cl channels and with K+ channels, through GTP-binding proteins. Brain Res. Mol. Brain Res. 8, 301-309. 

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