title: EGF and angiotensin II modulate lysophosphatidic acid LPA(1) receptor function and phosphorylation state.
abstract: BACKGROUND
  Lysophosphatidic acid (LPA) is a local mediator that exerts its actions through G protein coupled receptors. Knowledge on the regulation of such receptors is scarce to date. Here we show that bidirectional cross-talk exits between LPA(1) and EGF receptors.
  
  
  METHODS
  C9 cells expressing LPA(1) receptor fussed to the enhanced green fluorescent protein were used. We studied intracellular calcium concentration, Akt/PKB phosphorylation, LPA(1) and EGF receptor phosphorylation.
  
  
  RESULTS
  EGF diminished LPA-mediated intracellular calcium response and induced LPA(1) receptor phosphorylation, which was sensitive to protein kinase C inhibitors. Angiotensin II and LPA induced EGF receptor transactivation as evidenced by Akt/PKB phosphorylation through metalloproteinase-catalyzed membrane shedding of heparin-binding EGF and autocrine/paracrine activation of EGF receptors. This process was found to be of major importance in angiotensin II-induced LPA(1) receptor phosphorylation. Attempts to define a role for EGF receptor transactivation in homologous LPA(1) receptor desensitization and phosphorylation suggested that G protein-coupled receptor kinases are the major players in this process, overshadowing other events.
  
  
  CONCLUSIONS
  EGF receptors and LPA(1) receptors are engaged in an intense liaison, in that EGF receptors are capable of modulating LPA(1) receptor function through phosphorylation cascades. EGF transactivation plays a dual role: it mediates some LPA actions, and it modulates LPA(1) receptor function in inhibitory fashion.
  
  
  CONCLUSIONS
  EGF and LPA receptors coexist in many cell types and play key roles in maintaining the delicate equilibrium that we call health and in the pathogenesis of many diseases. The intense cross-talk described here has important physiological and pathophysiological implications.
authors.affiliation: Departmento de Biología Celular y Desarrollo, Instituto de Fisiologíca Celular, Universidad Naxional Autónoma de México, México.
authors.forename: Christian C
authors.initials: CC
authors.lastname: Colín-Santana
authors.forename: S Eréndira
authors.initials: SE
authors.lastname: Avendaño-Vázquez
authors.forename: Rocío
authors.initials: R
authors.lastname: Alcántara-Hernández
authors.forename: J Adolfo
authors.initials: JA
authors.lastname: García-Sáinz
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D047468:Immunoprecipitation; D010766:Phosphorylation; D051381:Rats; D049368:Receptors, Lysophosphatidic Acid / Q000378:metabolism*
chemical_list: D049368:Receptors, Lysophosphatidic Acid; D000804:Angiotensin II; D004815:Epidermal Growth Factor