Phosphorylation of atrial natriuretic factor R1 receptor by serine/threonine protein kinases: evidences for receptor regulation.
The 130 kDa atrial natriuretic factor receptor (ANF-R1) purified from bovine adrenal zona glomerulosa is phosphorylated in vitro by serine/threonine protein kinases such as cAMP-, cGMP-dependent and protein kinase C. This phosphorylation is independent of the presence of ANF (99-126) and there is no detectable intrinsic kinase activity associated with the ANF-R1 receptor or with its activated form. In bovine adrenal zona glomerulosa cells, TPA (phorbol ester) induces a marked inhibition of the ANF-stimulated cGMP accumulation as well as of the membrane ANF-sensitive guanylate cyclase catalytic activity without any change in the binding capacity or affinity for 125I-ANF. However, we have demonstrated a significant 32P incorporation in the ANF-R1 receptor of the TPA-treated cells. The effect of TPA on the zona glomerulosa ANF-R1 receptors was abolished by calphostin C, a specific protein kinase C inhibitor. Altered ANF actions due to blunted response of guanylate cyclase to ANF could be a consequence of the ANF receptor phosphorylation by excessive activity of protein kinase C and might be involved in the pathogenesis of hypertension.
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D001667:Binding, Competitive; D002417:Cattle; D006152:Cyclic GMP / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D008969:Molecular Sequence Data; D009281:Naphthalenes; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation; D011083:Polycyclic Compounds / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D017461:Receptors, Atrial Natriuretic Factor / Q000187:drug effects / Q000378:metabolism*; D015384:Zona Glomerulosa / Q000378:metabolism
D009281:Naphthalenes; D010703:Phorbol Esters; D011083:Polycyclic Compounds; D009320:Atrial Natriuretic Factor; D011493:Protein Kinase C; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP; C058819:calphostin C