Gα₁₄ links a variety of G_i‐ and G_s‐coupled receptors to the stimulation of phospholipase C

Abstract

The bovine Gα14 is a member of the Gq subfamily of G proteins that can regulate phospholipase Cβ isoforms but the extent to which Gα14 recognizes different receptor classes is not known. Gα14 was cotransfected with a variety of receptors in COS‐7 cells, and agonist‐induced stimulation of phospholipase C was then measured. Activation of the type 2 but not type 1 somatostatin receptor in cells coexpressing Gα14 stimulated the accumulation of inositol phosphates; functional expression of both subtypes of somatostatin receptors was determined by the ability of somatostatin to inhibit cyclic AMP accumulation. Among the three opioid receptors (μ, δ, and κ), only the δ receptor was capable of stimulating IP formation when coexpressed with Gα14 in COS‐7 cells. A panel of Gi‐ and Gs‐linked receptors was screened for their ability to stimulate IP accumulation via Gα14. The adenosine A1, complement C5a, dopamine D1, D2 and D5, formyl peptide, luteinizing hormone, secretin, and the three subtypes of melatonin (mt1, MT2, and Xenopus) receptors were all incapable of activating Gα14, while the α2‐ and β2‐adrenoceptors were able to do so. Gα14‐mediated stimulation of phospholipase Cβ was agonist dose‐dependent. These data demonstrate that although Gα14 can interact with different classes of receptors, it is much less promiscuous than Gα15 or Gα16. British Journal of Pharmacology (2001) 132, 1431–1440; doi:

Differential chemokine activation of CC chemokine receptor 1‐regulated pathways: ligand selective activation of Gα 14‐coupled pathways

“…The origins of the cDNA encoding CCR1, bovine G § 14 , human G § 16 , and the 16z44 chimera have been described [17,33,34]. Tissue culture reagents were purchased from Life Technologies (Gaithersburg, MD).…”

Activation of Nuclear Factor κB by Somatostatin Type 2 Receptor in Pancreatic Acinar AR42J Cells Involves Gα14 and Multiple Signaling Components

“…Indeed, previous findings have illustrated that SSTR2 can couple efficiently to G␣ 14 for inositol trisphosphate production (6). Moreover, the PLC␤ cascade has been demonstrated to play an important role in the regulation of NFB transcriptional activity (19).…”

“…Furthermore, modulation of the activities of tyrosine phosphatase and mitogen-activated protein kinases (MAPKs) by SSTR2 has been well documented (1). Recent studies suggest that SSTR2 can also employ other G proteins such as G 14 and G 16 for signal transduction (6,7). Its ability to interact functionally with G␣ 14 is particularly interesting.…”

“…It is particularly noteworthy that the adenosine A 1 receptor can employ G␣ 16 to activate NFB (15) because G␣ 14 and G␣ 16 are highly similar in terms of both their receptor and effector selectivities. Because SSTR2 can interact functionally with G␣ 14 (6), it may well be able to regulate NFB if G␣ 14 possesses the same capability as G␣ 16 .…”

Oncostatic effects of the indole melatonin and expression of its cytosolic and nuclear receptors in cultured human melanoma cell lines

“…The anticarcinogenic effect seems to be increased through membrane, cytosolic and/or nuclear receptors (45,47,52,53). The membrane receptors, represented by MT1 and MT2, belong to a G-protein coupled receptor super-family which can bind to a variety of G-proteins (54)(55)(56) and are differentially expressed in melanoma cell lines (24). Cytosolic NRH:quinone oxidoreductase 2 (NQO2, QR2) possesses melatonin binding sites previously described as MT3 receptor (57), differing in this aspect from NAD(P)H:quinone oxidoreductase 1 (NQO1, QR1) (58).…”