Regulatory subunit of cAMP-dependent protein kinase inhibits phosphoprotein phosphatase.
The activity of a purified high molecular weight phosphoprotein phosphatase was inhibited by purified type II cAMP-dependent protein kinase. This effect required cAMP and was obtained in the absence of ATP. The isolated type II regulatory subunits (R-subunits) from several species also inhibited the phosphatase activity in both crude extracts and purified preparations. Half maximal inhibition was observed at 0.06-0.25 microM, well within the physiological range of R-subunit concentrations. The inhibitory potency of R-subunit was greater using the thiophosphorylated form. Limited trypsinization of the R-subunit abolished the inhibitory activity. The C-subunit released the bound cAMP when combined with R-subunit, but the phosphatase did not, implying that the inhibited species is a R.cAMP-phosphatase complex. The results suggest that the R-subunit might have at least one physiological role in addition to inhibition of the C-subunit, i.e., inhibition of phosphatase. The latter would occur only when cAMP is elevated.
Khatra
B S
BS
Printz
R
R
Cobb
C E
CE
Corbin
J D
JD
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D006736:Horses; D046911:Macromolecular Substances; D008970:Molecular Weight; D009206:Myocardium / Q000201:enzymology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D011494:Protein Kinases / Q000378:metabolism*; D011817:Rabbits; D013045:Species Specificity; D013552:Swine; D013873:Thionucleotides / Q000378:metabolism
D046911:Macromolecular Substances; D013873:Thionucleotides; C022571:adenosine 5'-O-(3-thiotriphosphate); D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases