New signal transduction mechanisms of atrial natriuretic factor: inhibition of phosphorylation of protein kinase C and A 240 kDa protein in adrenal cortical plasma membrane by cGMP dependent and independent mechanisms.
The effects of synthetic atrial natriuretic factor (ANF) on the state of protein phosphorylation in plasma membranes of bovine adrenal cortex have been studied in vitro. ANF (1x10(-8)M - 1x10(-7)M) specifically inhibited the phosphorylation of two distinct proteins of 78 kDa and 240 kDa. Immunoblotting with specific antiserum to protein kinase C produced evidence that 78 kDa protein is most likely the protein kinase C whose phosphorylation is inhibited by both ANF and cGMP. However, cGMP did not affect the phosphorylation of 240 kDa protein, indicating a new cGMP-independent mechanism of ANF action in the adrenal, which is compatible with the lack of action of cGMP and its analogs in ANF-induced inhibition of aldosterone secretion from adrenal cortex. The inhibition of phosphorylation of putative protein kinase C by ANF or cGMP indicates a hitherto unknown signal transduction mechanism of ANF.
Pandey
K N
KN
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN 37232.
Inagami
T
T
Girard
P R
PR
Kuo
J F
JF
Misono
K S
KS
D000302:Adrenal Cortex / Q000378:metabolism*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D006152:Cyclic GMP / Q000494:pharmacology*; D007700:Kinetics; D008565:Membrane Proteins / Q000378:metabolism*; D008970:Molecular Weight; D010750:Phosphoproteins / Q000302:isolation & purification; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*
D008565:Membrane Proteins; D010750:Phosphoproteins; D009320:Atrial Natriuretic Factor; D011493:Protein Kinase C; D006152:Cyclic GMP