title: Involvement of GPR12 in the regulation of cell proliferation and survival.
abstract: GPR12, a member of the orphan G-protein-coupled receptor family, constitutively activates the Gs protein and increases intracellular cyclic AMP concentrations. GPR12 can be activated by its known ligand-sphingosylphosphorylcholine, which regulates cellular physiological activities, including proliferation, neurite extension, cell clustering, and maintenance of meiotic arrest. However, signaling pathways involved in the GPR12-mediated physiological and biochemical changes are still not clearly illustrated. In the present study, heterologous GPR12 expression was demonstrated to promote proliferation and survival in human embryonic kidney 293 cells. Immunochemical analysis showed that Ki67, a prototypic cell cycle-related nuclear protein, might participate in the regulation of GPR12-mediated cell proliferation. Activation of extracellular signal-regulated protein kinase signaling and increased total Erk1/2 and B-cell lymphoma/leukemia-2 expression were also observed in HEK293 cells overexpressing human GPR12. In addition, we found that GPR12 promoted cell survival under serum deprivation, indicating that GPR12 may play a role in cell proliferation and survival.
authors.affiliation: Institutes for Advanced Interdisciplinary Research, East China Normal University, 3663 North Zhongshan Road, Shanghai 200062, China.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Lu
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.forename: Bo
authors.initials: B
authors.lastname: Meng
authors.forename: Suzhen
authors.initials: S
authors.lastname: Dong
authors.forename: Yinghe
authors.initials: Y
authors.lastname: Hu
mesh_terms: D017209:Apoptosis; D049109:Cell Proliferation; D002470:Cell Survival; D016895:Culture Media, Serum-Free; D000242:Cyclic AMP / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D013312:Stress, Physiological; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D016895:Culture Media, Serum-Free; C097350:GPR12 protein, human; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D051028:bcl-2-Associated X Protein; D000242:Cyclic AMP; D048049:Extracellular Signal-Regulated MAP Kinases