Somatostatin-induced stimulation of a high-affinity GTPase in membranes of S49 lymphoma cyc- and H21a variants.
The influence of somatostatin was studied on GTPase activity in membranes of cyc- and H21a variants of S49 lymphoma cells, which are functionally defective in the guanine nucleotide site (Ns) mediating hormonal stimulation of the adenylate cyclase. Somatostatin, which inhibits adenylate cyclase in these membranes by a GTP-dependent process, caused a concomitant activation of a high-affinity GTPase (apparent Km approximately equal to 0.2 microM) by 40-50%. The hormone-stimulated GTPase also exhibited an apparent Km value of about 0.2 microM. GTPase stimulation by somatostatin occurred without an apparent lag phase. There was a close correlation between adenylate cyclase inhibition and high-affinity GTPase stimulation induced by somatostatin. Various other peptide hormones studied and isoproterenol had no effect on GTP hydrolysis. Activation of the enzyme by somatostatin was reduced or abolished by pretreatment of the membranes with the SH reagent, N-ethylmaleimide. In membranes of wild-type S49 lymphoma cells, somatostatin caused an increase in GTPase activity similar to that in cyc- and H21a membranes. The data show that cyc- and H21a membranes, which are more or less defective in Ns, contain a hormone-sensitive, high-affinity GTPase and that the activation of this enzyme is closely related to adenylate cyclase inhibition by somatostatin. The data suggest that, similar to Ns, the activity state of the guanine nucleotide site (Ni), which apparently mediates somatostatin-induced inhibition of the adenylate cyclase, is controlled by a high-affinity GTPase.
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004789:Enzyme Activation / Q000187:drug effects; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006868:Hydrolysis; D007700:Kinetics; D008223:Lymphoma / Q000201:enzymology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000201:enzymology; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D011485:Protein Binding; D013004:Somatostatin / Q000494:pharmacology*
D000067956:Adenylyl Cyclase Inhibitors; D013004:Somatostatin; D010744:Phosphoric Monoester Hydrolases; D020558:GTP Phosphohydrolases