The G-protein-coupled receptor GCR1 regulates DNA synthesis through activation of phosphatidylinositol-specific phospholipase C.
Different lines of evidence suggest that specific events during the cell cycle may be mediated by a heterotrimeric G-protein activated by a cognate G-protein coupled receptor. However, coupling between the only known Galpha-subunit of the heterotrimeric G-protein (GPA1) and the only putative G-protein coupled receptor (GCR1) of plants has never been shown. Using a variety of approaches, we show here that GCR1-enhanced thymidine incorporation into DNA depends on an increase in phosphatidylinositol-specific phospholipase C activity and an elevation of inositol 1,4,5-trisphosphate levels in the cells. Tobacco (Nicotiana tabacum) cells that overexpress either Arabidopsis GCR1 or GPA1 display this phenomenon. We suggest on the basis of these results that GCR1-controlled events during the cell cycle involve phosphatidylinositol-specific phospholipase C as an effector of GCR1 and inositol 1,4,5-trisphosphate as a second messenger, and that GCR1 and GPA1 are both involved in this particular signaling pathway.
Apone
Fabio
F
Arena Pharmaceuticals, 6166 Nancy Ridge Drive, San Diego, California 92121, USA.
Alyeshmerni
Nicole
N
Wiens
Kathryn
K
Chalmers
Derek
D
Chrispeels
Maarten J
MJ
Colucci
Gabriella
G
D029681:Arabidopsis Proteins / Q000378:metabolism*; D003001:Cloning, Molecular; D004261:DNA Replication / Q000235:genetics*; D018744:DNA, Plant / Q000096:biosynthesis; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D008954:Models, Biological; D043265:Phosphatidylinositol Diacylglycerol-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054801:Phosphoinositide Phospholipase C; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D013936:Thymidine / Q000378:metabolism; D014026:Nicotiana / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D029681:Arabidopsis Proteins; D018744:DNA, Plant; D004791:Enzyme Inhibitors; D004963:Estrenes; C112029:GCR1 protein, Arabidopsis; D011760:Pyrrolidinones; D043562:Receptors, G-Protein-Coupled; D011994:Recombinant Proteins; D014157:Transcription Factors; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D015544:Inositol 1,4,5-Trisphosphate; D011493:Protein Kinase C; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D013936:Thymidine