G protein G?q/11 and G?i1,2 are activated by pancreastatin receptors in rat liver: Studies with GTP-?35S and azido-GTP-?-32P

Abstract

In the liver, pancreastatin exerts a glycogenolytic effect through interaction with specific receptors, followed by activation of phospholipase C and guanylate cyclase. Pancreastatin receptor seems to be coupled to two different G protein systems: a pertussis toxin-insensitive G protein that mediates activation of phospholipase C, and a pertussis toxin sensitive G protein that mediates the cyclic GMP production. The aim of this study was to identify the specific G protein subtypes coupling pancreastatin receptors in rat liver membranes. GTP binding was determined by using gamma-35S-GTP; specific anti-G protein alpha subtype sera were used to block the effect of pancreastatin receptor activation. Activation of G proteins was demonstrated by the incorporation of the photoreactive GTP analogue 8-azido-alpha-32P-GTP into liver membranes and into specific immunoprecipitates of different Galpha subunits from soluble rat liver membranes. Pancreastatin stimulation of rat liver membranes increases the binding of gamma-35S-GTP in a time- and dose-dependent manner. Activation of the soluble receptors still led to the pancreastatin dose-dependent stimulation of gamma-35S-GTP binding. Besides, WGA semipurified receptors also stimulates GTP binding. The binding was inhibited by treatment with anti-Galphaq/11 (85%) and anti-Galphai1,2 (15%) sera, whereas anti-Galphao,i3 serum failed to affect the binding. Finally, pancreastatin stimulates GTP photolabeling of particulate membranes. Moreover, it specifically increased the incorporation of 8-azido-alpha-32P-GTP into Galphaq/11 and Galpha, but not into Galphao,i3 from soluble rat liver membranes. In conclusion, pancreastatin stimulation of rat liver membranes led to the activation of Galphaq/11 and Galphai1,2 proteins. These results suggest that Galphaq/11 and Galphai1,2 may play a functional role in the signaling of pancreastatin receptor by mediating the production of IP3 and cGMP respectively.

Differential G protein subunit expression by prostate cancer cells and their interaction with CXCR5

“…The ability of GPCRs to differentially couple to multiple classes of G proteins (G αi , G αq/11 , G α12/13 ) has also been described for sphingosine-1-phosphate receptors, and the liver pancreastatin receptor [40,41]. While the possibility of CXCR5 switching from G αi to G α13 signaling pathways requires further investigation, the possibility of its occurrence presents a means for tumor cells to acquire new signaling machinery that could promote disease progression.…”

Natural Inflation with a periodic non-minimal coupling

“…In other words, any coupling to R which is non-derivative in φ should vanish if V (φ) goes to zero. A similar logic of adding shift symmetric corrections to NI was also proposed in [2], using only derivative interactions, and in [3], using non-standard kinetic terms.…”

Discovery of a Novel Target for the Dysglycemic Chromogranin A Fragment Pancreastatin: Interaction with the Chaperone GRP78 to Influence Metabolism

“…A putative PST receptor was purified from rat liver membranes by Sanchez-Margalet et al, and may be physically associated with a Gαq/11 protein [19]; however the final identification and sequencing of such a PST receptor have been elusive so far. PST seems to activate a receptor signaling pathway that is typically associated with seven-spanning transmembrane receptors coupled to Gq-PLCβ-calcium-PKC signaling and mediated through protein kinase C and NO-dependent pathways [20]–[23]. Increased PST plasma levels, correlating with catecholamine levels have been found in insulin resistant states such as gestational diabetes, essential hypertension or type 2 diabetes mellitus [24]–[27].…”