Guanine nucleotide regulatory protein activation

Lefkowitz, RJ, Cotecchia, S, Samama, P and Costa, T (1993) Constitutive activity of receptors coupled to guanine nucleotide regulatory proteins. TIPS 14 303-307. 

Anand-Srivastava MB. 1993. Rat platelets from spontaneously hypertensive rats exhibit decreased expression of inhibitory guanine nucleotide regulatory protein relationship with adenylate cyclase activity. Circ Res 173 1032-1039. 

Susani EE, Manders WT, Knight DR, Vatner DE, Vatner SF, Homey CJ. 1989. One hour of myocardial ischemia decreases the activity of the stimulatory guanine-nucleotide regulatory protein Gs. Circ Res 65 1145-1150. 

Other evidence for the involvement of a G-protein in the action of insulin has come from studies by Walaas and co-workers [104]. They have demonstrated that insulin stimulated the activity of a cyclic AMP-dependent protein kinase activity in sarcolemma membranes. As this effect of insulin was enhanced if micromolar concentrations of GTP-binding protein were present, they suggested that a guanine nucleotide regulatory protein was involved in the hormonal control of this kinase. Indeed, cholera toxin also appeared to obliterate this action of insulin, as it did the effect of insulin on liver adenylate cyclase and the peripheral plasma membrane cyclic AMP phosphodiesterase in liver. 

Verghese, M. W., Smith, C. D., and Snyderman, R. (1986). Role of guanine nucleotide regulatory protein in polyphosphoinositide degradation and activation of phagocytic leukocytes by chemoattractants. J. Cell Biochem. 32, 59-69. 

Figure 2.13. Histamine H,-receptor-mediated inositol phospholipid hydrolysis. Stimulation of H,-receptors leads to activation of a phospholipase C. probably via a guanine-nucleotide regulatory protein (N). which catalyses the hydrolysis of phosphatidylinositol 4.5 -bisphosphate (PIP2) to give inositol trisphosphate (IP3) and 1,2-diacylglycerol (DG). IP3 is then broken down by phosphatases to eventually yield free myo-inositol. Lithium ions can inhibit the conversion of inositol 1-phosphate (IP,) to myo-inositol. Free inositol then interacts with CDP-diacylglycerol,formed by a reaction between phosphatidic acid (PA) and CTP, to yield phosphatidylinositol (PI). Phosphorylation of PI by kinases completes the lipid cycle by reforming PIP2. Modified from [147,148].

Verghese, M.W., Charles, L., Jakoi, L., Dfllon, S.B. and Snyderman, R. (1987). Role of a guanine nucleotide regulatory protein in the activation of phospholipase C by different chemoattractants. /. Immunol. 138, 4374-M380. 

One of the earliest effects found for PGEj was its ability to inhibit epinephrine-induced lipolysis in adipocytes by preventing the accumulation of cAMP ". The ability of PGEj to blunt isoproterenol-induced increases in cAMP in hamster adipocytes was subsequently shown to be reduced in hamsters that had been treated with a crude source of pertussis toxin. More recently, Murayama and Ui demonstrated that pertussis toxin treatment of adipocytes also diminishes the ability of PGEj to cause a GTP-dependent inhibition of adenylate cyclase activity in membranes prepared from these cells associated with this latter effect is a pertussis toxin-dependent, ADP-ribosylation of a protein subunit having the characteristic size (M = 41000) of the subunit of the inhibitory guanine nucleotide regulatory protein N. ... 

Houslay, M.D., Bojanic, D. and Wilson, A. (1986). Platelet activating factor and U44069 stimulate a GTPase activity in human platelets which is distinct from the guanine nucleotide regulatory proteins, N, and Nj. Biochem ]., 234, 737-740... 

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.

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