Regulation of sarcolemmal Ca2+ pump by endogenous protein phosphatases.
The function of several key sarcolemmal proteins is modulated through phosphorylation-dephosphorylation of serine/threonine residues. While the involvement of sarcolemma-associated protein kinases in the phosphorylation of these proteins has been established, the nature of the protein phosphatases controlling these proteins has not been investigated. Rat heart sarcolemma contains two protein phosphatase isozymes, protein phosphatase 1 and 2A, which are distinguished on the basis of their susceptibility of inhibitor 2. Both isozymes elute from a Bio Gel A-0.5 column in association with the highest molecular weight protein fraction. However, some protein phosphatase 1 activity elutes with a smaller molecular weight fraction of about 37,000, suggesting that the native enzyme exists as a catalytic subunit in complex with an anchor protein. Inhibition of the protein phosphatases using standard inhibitors leads to a stimulation in both the rate and extent of 32P incorporation into isolated sarcolemma. Also affected by inhibition of protein phosphatase activity is the rate of ATP-dependent calcium uptake, which is stimulated following exposure to either inhibitor 2, a classical protein phosphatase 1 inhibitor, and microcystin, a protein phosphatase 1 and 2A inhibitor. The data suggest that the protein phosphatases regulate the dephosphorylation of sarcolemmal proteins. Through this mechanism they serve as important modulators of the sarcolemmal Ca2+ pump.
Department of Pharmacology, School of Medicine, University of South Alabama.
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Schaffer
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Punna
D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000502:physiology*; D002850:Chromatography, Gel; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D051381:Rats; D012508:Sarcolemma / Q000201:enzymology*
D009124:Muscle Proteins; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D000252:Calcium-Transporting ATPases; D002118:Calcium