The role of autophosphorylation of cAMP-dependent protein kinase II in the inhibition of protein phosphatase-1.
1. The inhibition of the catalytic subunit of protein phosphatase-1 (PP-1c) by the regulatory subunit of cAMP-dependent protein kinase II (RII) was studied. 2. Phosphorylation or thiophosphorylation of RII increased its inhibitory potency up to 4- and 6-fold and rendered it competitive with respect to the substrate of PP-1c, phosphorylase a. The Ki values for thiophospho-RII and phospho-RII were 200 and 500 nM, respectively. 3. Though PP-1c was able to release phosphate from phospho-RII, its activity once incubated with phospho-RII, remained inhibited even 80% of the phosphate was released from phospho-RII. 4. The catalytic subunit of cAMP-dependent protein kinase was effective in suspending the inhibition employed either before or after the addition of phospho-RII to PP-1c. 5. No exclusive bindings of thiophospho-RII and heat-stable protein inhibitors to the PP-1c could be proved by double inhibition studies, however some synergism was observed in their effect.
Vereb
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Department of Medical Chemistry, University Medical School, Debrecen, Hungary.
Gergely
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D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism* / Q000502:physiology; D054645:Protein Phosphatase 1; D011506:Proteins / Q000378:metabolism; D000097847:Protein Phosphatase Inhibitory Proteins
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010749:Phosphoprotein Phosphatases; D011494:Protein Kinases; D054645:Protein Phosphatase 1; D011506:Proteins; C015482:protein kinase modulator; C021042:protein phosphatase inhibitor-1; C024833:protein phosphatase inhibitor-2; D000097847:Protein Phosphatase Inhibitory Proteins