Human Phosphatidylethanolamine-binding Protein Facilitates Heterotrimeric G Protein-dependent Signaling

Abstract

In this study we report that human phosphatidylethanolamine-binding protein (hPBP) facilitates heterotrimeric G protein-coupled signaling. In Xenopus laevis oocytes, coexpression of hPBP with human opioid receptor, human ␦ opioid receptor, or human somatostatin receptor 2 evoked an agonist-induced increase in potassium conductance of G protein-activated inwardly rectifying potassium channels. This activation of heterotrimeric G protein signaling in oocytes could also be elicited by injection of bacterially overexpressed and purified hPBP. Stimulatory effect was pertussis toxinsensitive and present even in the absence of coexpressed receptors. Additionally, an increase in G protein-mediated inhibition of adenylate cyclase activity, measured by the inhibition of forskolin-mediated cAMP accumulation, could be detected in HEK293 and NIH3T3 cells after expression of hPBP and in Xenopus oocytes after injection of hPBP. As

Raf Kinase Inhibitor Protein (RKIP) Dimer Formation Controls Its Target Switch from Raf1 to G Protein-coupled Receptor Kinase (GRK) 2

“…As controls, we used either mock-transfected cells or cells transfected with N-terminal RKIP fragments, which did not contain the loop sequence (supplemental Fig. S4, A (RKIP [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] ) and C (RKIP )). In accordance with our previous results, prevention of RKIP dimerization by loop 127-150 was accompanied by inhibition of PKC-induced RKIP-GRK2 assembly (Fig.…”

“…The Raf kinase inhibitor protein (RKIP) 3 modulates and controls crucial intracellular signaling networks, including the signaling cascades of Raf/MEK/ERK, NFB, glycogen synthase kinase-3␤, and G protein-coupled receptors (GPCRs) (1)(2)(3)(4)(5). RKIP belongs to the evolutionarily conserved phosphatidylethanolamine-binding protein (PEBP) family, which is characterized by the ability to bind phospholipids in vitro (6,7).…”

Proteomic Analysis of Membrane-Associated Proteins from Rat Liver Autophagosomes

“…Both of these pathways have been implicated in the regulation of autophagy. [62][63][64] Furthermore, PEBP has been shown to facilitate signaling through trimeric G-proteins, 65 which are also involved in autophagy control, 66 possibly through its ability to inhibit, after phosphorylation at Ser-153, the protein kinase GRK-2 that inactivates G-protein-coupled receptors. 67 PEBP, could, conceivably, also regulate autophagy by controlling the availability of PE for conjugation with the essential autophagy protein, Atg8/LC3.…”

Raf kinase inhibitory protein knockout mice: Expression in the brain and olfaction deficit

“…For example, the inhibition of RKIP-1 enhances NF-κB-induced transcription while over-expression reduces it [40]. In addition, RKIP-1 impinges on GPCR signaling by controlling the activity of the G-protein coupled receptor kinase-2 (GRK2) [21,23].…”