Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Small G-proteins (SMGs) require isoprenylation for their association with membranes. We have examined protein isoprenylation, subcellular distribution of SMGs, cytosolic Ca2+ changes and insulin secretion in HIT-T15 cells after treatment with lovastatin, which inhibits the production of isoprenoids by blocking mevalonate production by 3-hydroxy-3-methylglutaryl-CoA reductase. Numerous proteins in the 20-70 kDa range were found to be isoprenylated. Most of these proteins co-migrated with SMGs (21-27 kDa). Lovastatin treatment (25 microM, 24 h) decreased protein isoprenylation and affected the distribution of several SMGs, causing a large accumulation in the cytosol and a detectable decrease in membranes. Lovastatin selectively attenuated the potentiating action of bombesin and vasopressin, which activate phospholipase C in these cells, on insulin secretion stimulated by nutrients (glucose + leucine + glutamine). This lovastatin effect was overcome by mevalonate. Insulin secretion stimulated by nutrients alone or insulin release in the presence of the potentiating agents forskolin or phorbol myristate acetate remained unaffected. As the modulation of insulin secretion by isoprenaline and somatostatin were not altered by lovastatin, the drug does not non-selectively affect the binding of ligands to their receptors. Lovastatin did not interfere with the activation of phospholipase C by bombesin and vasopressin, since the rise in cytosolic Ca2+ induced by these agents was not changed. Limonene, proposed to block specifically prenyl-protein transferases of SMGs, did not alter protein isoprenylation patterns, but inhibited the stimulated insulin secretion. In conclusion, lovastatin selectively attenuated the potentiation of nutrient-induced insulin secretion by bombesin and vasopressin without affecting their activation of phospholipase C. The concomitant changes in SMG isoprenylation and their subcellular distribution after lovastatin treatment suggest that SMGs could play an important role in the bombesin and vasopressin action on insulin secretion.
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PMID:Blockade of mevalonate production by lovastatin attenuates bombesin and vasopressin potentiation of nutrient-induced insulin secretion in HIT-T15 cells. Probable involvement of small GTP-binding proteins. 842 83

cAMP-mediated cell proliferation is a complex process that involves multiple pathways. Using a cAMP-dependent cell system, FRTL-5 thyroid cells, we have previously demonstrated the existence of a precise autocrine loop in the control of cell proliferation that involves the positive effector thyrotropin (TSH) and the general inhibitor somatostatin. In search of the regulatory mechanisms responsible for the TSH and somatostatin control of cell proliferation, we analyzed the cell cycle regulatory proteins and the cellular pathways involved in the action of both signals. The results show that specific inhibition of cAMP-dependent protein kinase (PKA) and phosphatidylinositol (PI) 3-kinase blocks independently TSH-induced FRTL-5 cell proliferation and that somatostatin interferes with both signals. Each pathway activates different proteins required for G(1)/S progression. Thus, PKA is responsible for the TSH-induction of 3-hydroxy-3-methylglutaryl-CoA reductase mRNA levels, RhoA activation, and down-regulation of p27(kip1). These correlated events are necessary for FRTL-5 cell proliferation after TSH stimulation. Moreover, TSH through PKA pathway increases cyclin-dependent kinase 2 levels, whereas PI 3-kinase signaling increases cyclin E levels. Together, both pathways finally converge, increasing the formation and activation of cyclin E x cyclin-dependent kinase 2 complexes and the phosphorylation of the retinoblastoma protein, two important steps in the transition from G(1) to S phase in growth-stimulated cells. Somatostatin exerts its antiproliferative effect inhibiting more upstream the TSH stimulation of PKA and PI 3-kinase, interfering with the TSH-mediated increases of intracellular cAMP levels by inactivation of adenylyl cyclase activity. Together, these results suggest the existence of a PKA-dependent pathway and a new PKA-independent PI 3-kinase pathway in the TSH/cAMP-mediated proliferation of FRTL-5 thyroid cells.
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PMID:Somatostatin interferes with thyrotropin-induced G1-S transition mediated by cAMP-dependent protein kinase and phosphatidylinositol 3-kinase. Involvement of RhoA and cyclin E x cyclin-dependent kinase 2 complexes. 1080 88