Phosphorylation and desensitization of the lysophosphatidic acid receptor LPA1.
In C9 cells, LPA (lysophosphatidic acid) induced inositol phosphate production, increased intracellular calcium concentration and inhibited adenylate cyclase activity. These responses were abolished in cells challenged with active phorbol esters. Action of phorbol esters was blocked by inhibitors of PKC (protein kinase C) and by its down-regulation. LPA1 receptor phosphorylation was observed in response to phorbol esters. The effect was rapid (t1/2 approximately 1 min), intense (2-fold) and sustained (at least 60 min). PKC inhibitors markedly decreased the LPA1 receptor phosphorylation induced by phorbol esters. LPA1 receptor tagged with the green fluorescent protein internalized in response to PKC activation. In addition, LPA and angiotensin II were also capable of inducing LPA1 receptor phosphorylation, showing that LPA1 receptor can be subjected to homologous and heterologous desensitization.
Avendaño-Vázquez
S Eréndira
SE
Departamento de Biología Celular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-248, México, DF 04510, México.
García-Caballero
Agustín
A
García-Sáinz
J Adolfo
JA
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002460:Cell Line; D004705:Endocytosis / Q000187:drug effects; D004847:Epithelial Cells; D015870:Gene Expression; D020962:Heterotrimeric GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D047468:Immunoprecipitation; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D037342:Pertussis Toxin / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D008246:Lysophospholipids; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D049368:Receptors, Lysophosphatidic Acid; D000804:Angiotensin II; D037342:Pertussis Toxin; D011493:Protein Kinase C; D020962:Heterotrimeric GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; C032881:lysophosphatidic acid; D002118:Calcium