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Phosphorylation of atrial natriuretic factor R1 receptor by serine/threonine protein kinases: evidences for receptor regulation

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Abstract

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.

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Abbreviations

ANF:

Atrial Natriuretic Factor

ANF-R1 :

Atrial Natriuretic Factor Receptor, subtype 1

ATP:

Adenosine Triphosphate

CaCl2 :

Calcium Chloride

cAMP:

Adenosine cyclic 3′,5′-Monophosphate acid

cGMP:

Guanosine cyclic 3′5′-Monophosphate acid

EDC:

1-Ethyl-3-[3-Dimethylaminopropyl] Carbodiimide

EDTA:

Ethylenediaminetetraacetic Acid

GTP:

Guanosine Triphosphate

IBMX:

3-isobutyl-1-methylxanthine

kDa:

Kilodaltons

MgCl2 :

Magnesium Chloride

MgAC:

Magnesium Acetate

NaCl:

Sodium Chloride

PAGE:

Polyacrylamide Gel Electrophoresis

PKA:

cAMP-dependent protein kinase

PKG:

cGMP-dependent Protein Kinase

PKC:

Calcium/Phospholipid-dependent Protein Kinase

RIA:

Radioimmunoassay

SDS:

Sodium Dodecyl Sulfate

SHR:

Spontaneously Hypertensive Rat

Tris HCl:

Tris (Hydroxymethyl) aminomethane Hydrochloride

TPA:

12-O-Tetradecanoyl-Phorbol-13-Acetate

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Authors and Affiliations

  1. Laboratory of Molecular Pharmacology, Clinical Research Institute of Montreal, Department of Pharmacology and Faculty of Pharmacy, University of Montreal, Montreal, Canada

    L. Larose, J. -J. Rondeau, H. Ong & A. De Léan

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  1. L. Larose
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  2. J. -J. Rondeau
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  3. H. Ong
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  4. A. De Léan
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Larose, L., Rondeau, J.J., Ong, H. et al. Phosphorylation of atrial natriuretic factor R1 receptor by serine/threonine protein kinases: evidences for receptor regulation. Mol Cell Biochem 115, 203–211 (1992). https://doi.org/10.1007/BF00230332

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  • DOI: https://doi.org/10.1007/BF00230332

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