By G proteins

Table 13,1 Examples of physiological processes mediated by G proteins...

Adenylyl Cyclases. Figure 4 Regulation of adenylyl cyclases by G-proteins. Abbreviations Hs, Hj, Rs, and Rj denote hormones and receptors that lead to stimulation or inhibition, respectively, of adenylyl cyclases, Ca and Ci are active and inactive configurations of adenylyl cyclase, Fo forskolin binding site, Gs and Gj are GTP-dependent regulatory proteins comprising their respective as, and (3y subunits. 

Melanin-concentrating hormone (MCH) is a cyclic neuropeptide of 19 amino acids. It is involved in the modulation of feeding behavior. Its actions are mediated by G-protein coupled receptors (MCH1 and MCH2). 

Neuromedin U is a neuropeptide which is widely distributed in the gut and central nervous system. Peripheral activities of neuromedin U include stimulation of smooth muscle, increase in blood pressure, alteration of ion transport in the gut, control of local blood flow and regulation of adrenocortical function. The actions of neuromedin U are mediated by G-protein coupled receptors (NMU1, NMU2) which are coupled tO Gq/11. 

The 3 isozymes are activated by G protein-coupled receptors through two different mechanisms [2]. The first involves activated a-subunits of the Gq family of heterotrimeric G proteins (Gq, Gn, Gi4, G15/16). These subunits activate the (31, (33 and (34 PLC isozymes through direct interaction with a sequence in the C terminus. The domain on the Gqa-subunit that interacts with the (3 isozymes is located on a surface a-helix that is adjacent to the Switch III region, which undergoes a marked conformational change during activation. The second mechanism of G protein activation of PLC 3 isozymes involves (3y-subunits released from Gi/0 G proteins by their pertussis toxin-sensitive activation by certain receptors. The 3y-subunits activate the 32 and 33 PLC isozymes by interacting with a sequence between the conserved X and Y domains. 

In sympathetically innervated tissues, such as vas deferens or blood vessels, ATP produces fast responses mediated by P2X receptors followed by a slower component mediated by G protein-coupled a-adrenoceptors (Fig. 2) NPY usually acts as a pre-or postjunctional modulator of the release and/or action of NA and ATP. Similarly, for parasympathetic nerves supplying the urinary bladder, ATP provokes a fast, short-lasting twitch response via P2X receptors, whereas the slower component is mediated by G... 

Somlyo AP, Somlyo AV (2000) Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II. J Physiol 522 (Pt 2) 177-185... 

Bohm SK, Grady EF, Bunnett NW (1997) Regulatory mechanisms that modulate signalling by G-protein-coupled receptors. Biochem J 322 1-18... 

Luttrell LM (2006) Transmembrane signaling by G protein-coupled receptors. Methods Mol Biol 332 3—49... 

Prenzel N, Zwick E, Daub H et al (1999) EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. Nature 402 884-888... 

Figure 1. Simplified schematic of receptor-mediated signal transduction in neutrophils. Binding of ligand to the receptor activates a guanine-nucleotide-binding protein (G protein), which then stimulates phospholipase C. Phosphatidylinositol 4,5-bis-phosphate is cleaved to produce diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). DAG stimulates protein kinase C. IP3 causes the release of Ca from intracellular stores, which results in an increase in the cytosolic Ca concentration. This increase in Ca may stimulate protein kinase C, calmodulin-dependent protein kinases, and phospholipase A2. Protein phosphorylation events are thought to be important in stimulating degranulation and oxidant production. In addition, ionic fluxes occur across the plasma membrane. It is possible that phospholipase A2 and ionic channels may be governed by G protein interactions. ...

Bondensgaard K, Ankersen M, Thogersen H, Hansen BS, Wulff BS, Bywater RP. Recognition of privileged structures by G-protein coupled receptors. J Med Chem 2004 47 888-99. 

Wetzel MA, Steele AD, Eisenstein TK, Adler MW, Henderson EE, Rogers TJ (2000) Mu-opioid induction of monocyte chemoattractant protein-1, RANTES, and IFN-gamma-inducible protein-10 expression in human peripheral blood mononuclear cells. J Immunol 165 6519-6524 Widmer U, Manogue KR, Cerami A, Sherry B (1993) Genomic cloning and promoter analysis of macrophage inflammatory protein (MIP)-2, MIP-1 alpha, and MIP-1 beta, members of the chemokine superfamily of proinflammatory cytokines. J Immunol 150 4996-5012 Ye RD (2001) Regulation of nuclear factor kappaB activation by G-protein-coupled receptors. [Review] [136 refs]. J Leukoc Biol 70 839-848... 

Brown, DA (2000) The acid test for resting potassium channels. Curr. Biol. 10 R456-R459. Dolphin, AC (1998) Mechanisms of modulation of voltage-dependent calcium channels by G proteins. J. Physiol. 506 3-11. 

Hille, B (1994) Modulation of ion channel function by G protein-coupled receptors. Trends Neurosci. 17 531-536. 

Xiang Y, Li Y, Zhang Z, et al. Nerve growth cone guidance mediated by G protein-coupled receptors. Nat Neurosci 2002 5 843-848. 

In Chapter 1 (Section 1.2.4.3), the Hill equation and the Hill coefficient, nH, are described. Hill coefficients greater than or less than unity are often interpreted as indicating positive or negative cooperativity, respectively, in the relationship between receptor occupancy and response. For example, positive cooperativity could arise due to amplification in a transduction mechanism mediated by G-proteins and changes in cell calcium concentration. 

Effects mediated by G-protein coupled receptors (GPCRs) are very much slower than those mediated by, for example, ligand-gated ion channels, primarily because more steps are involved between activation of the receptor and the final response. For example, even in a simple, three-step, G-protein-mediated effect, such as the opening of atrial GIRK channels following the activation of M2 muscarinic receptors by acetylcholine, which follows the scheme ... 

Birnbaumer, L., Transduction of receptor signal into modulation of effector activity by G-proteins the first 20 years or so, FASEB /., 4, 3068-3078, 1990. 

Agonist-dependent desensitization of the kappa opioid receptor by G protein receptor kinase and beta-arrestin. J Biol Chem 1999 274 233802-233807. 

Kofuji, R, Davidson, N. and Lester, H. Evidence that neuronal G-protein-gated inwardly rectifying K+ channels are activated by G protein Py subunits and function as... 

Reports that AA is released primarily by G-protein-mediated PLA2 activation remain to be confirmed [84, 85]. In addition, modulation of PLA2 by Ca2+ and protein kinase needs to be better defined. It is clear that NMDA receptor activation promotes the release of AA [86], and that a variety of eicosanoids are then generated (Fig 33-2,33-3). The modulatory events that channel AA towards specific eicosanoids are not understood. The endocannabinoid family of lipid messengers will remain an active focus of interest because of the growing evidence of their actions in synaptic function, learning, memory, and other forms of behavior [56,87]. 

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