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Biomedical subjects

M A Kirchberger

Publications and source records attributed to M A Kirchberger.

At least 19 recordsLinked to original sources
PubMed1989

Modulation by polyelectrolytes of canine cardiac microsomal calcium uptake and the possible relationship to phospholamban.

Calcium uptake and (Ca2+ + Mg2+)-ATPase activity in canine cardiac microsomes were found to be stimulated by heparin and various other polyanions. Prior treatment of the microsomes with the ionophores alamethicin or A23187 produced no change in the extent of stimulation of the ATPase activity by heparin yet eliminated net calcium uptake. This finding and a lack of change in the stoichiometric ratio of mol of calcium transported/mol of ATP hydrolyzed (calcium:ATP) suggest that the effect of heparin is on the calcium pump rather than on a parallel calcium efflux pathway. Certain polycationic compounds including poly-L-arginine and histone inhibited both cardiac and fast skeletal muscle microsomal calcium uptake and also produced no change in the stoichiometric ratio of calcium to ATP. Several lines of evidence indicate that the polyanionic compounds tested stimulate calcium uptake by interacting with phospholamban, the putative phosphorylatable regulator of the cardiac sarcoplasmic reticulum calcium pump, whereas polycationic compounds appear to interact with the pump. (i) Heparin stimulated calcium uptake to the same extent as protein kinase A or trypsin, whereas prior phosphorylation or tryptic cleavage of phospholamban from the membrane abolished the stimulatory effect of heparin. (ii) Calcium uptake and (Ca2+ + Mg2+)-ATPase activity in fast skeletal muscle microsomes, which lack phospholamban, were unaffected by heparin. (iii) Purified cardiac (Ca2+ + Mg2+)-ATPase activity was no longer stimulated by heparin yet was still inhibited by polycationic compounds. The heparin-induced stimulation of calcium uptake was dependent on the pH and ionic strength of the heparin-containing preincubation medium, hence electrostatic interactions appear to play a significant role in heparin's stimulatory action. The data are consistent with an inhibitory role of the positively charged cytoplasmic domain of phospholamban with respect to calcium pump activity and the relief of the inhibition upon reduction in phospholamban's positive charge by phosphorylation or binding of polyanions.

Adenosine Triphosphatases↗
PubMed1989

Polyphosphoinositide formation in isolated cardiac plasma membranes.

Phosphatidylinositol (PtdIns) and phosphatidylinositol 4-phosphate (PtdIns4P) kinase activities in plasma membranes isolated from canine left ventricle were partially characterized, and their sensitivity to a number of intracellular variables was established. PtdIns and PtdIns4P kinase activities were estimated by the formation of [32P]PtdIns4P and [32P]phosphatidylinositol 4,5-bisphosphate ([32P]PtdIns(4,5)P2), respectively, when membranes were incubated with [gamma-32P]ATP and 0.1% Triton X-100. Unlike [32P]PtdIns4P formation [32P]PtdIns(4,5)P2 formation required exogenous (PtdIns4P) substrate. [32P]PtdIns4P and [32P]PtdIns(4,5)P2 formation were insensitive to Ca2+ at concentrations ranging from 0.1-30 microM. The hydrolysis of [32P]PtdIns4P was less than 15% under standard assay conditions for measuring its formation, and was unaffected by any of the variables tested. The apparent Km of the PtdIns kinase for ATP was 53 +/- 13 (S.E.M.) microM (N = 3). ADP inhibited [32P]PtdIns4P formation competitively with respect to ATP, the Ki being 0.4 mM. The data indicate that ADP is a poor competitive inhibitor of PtdIns kinase at the concentrations which are believed to be present intracellularly normally or which may be attained during mild hypoxia provided ATP levels are maintained in the millimolar range. Hence, any response of the myocardium to alpha-adrenergic hormones during mild hypoxia would be largely unimpaired by effects of Ca2+ on PtdIns and PtdIns(4,5)P2, or of ADP on PtdIns kinase activity.

1-Phosphatidylinositol 4-Kinase↗
PubMed1988

Differences in calcium uptake in native canine cardiac microsomes are correlated with the ratio of unphosphorylated to phosphorylated phospholamban as determined by Western blot analysis.

Phospholamban (PLM) is detectable by Western blot analysis of canine cardiac microsomes using rabbit antiserum against a peptide containing the 2 to 30 amino acid sequence of PLM. Phosphorylated PLM is distinguishable from the unphosphorylated form by virtue of a reduced electrophoretic mobility. Utilizing digital image analysis to determine relative band densities, it was found that the ratio of unphosphorylated to phosphorylated PLM is correlated with the rate of calcium uptake in 5 preparations of native microsomes (r = 0.94, p less than 0.01). The present analysis may be useful for determining the phosphorylation state of PLM in microsomes obtained from animals in physiological states characterized by impaired sarcoplasmic reticulum calcium pump activity.

Adenosine Triphosphate↗
PubMed1988

Presence of a Ca2+-sensitive CDPdiglyceride-inositol transferase in canine cardiac sarcoplasmic reticulum.

Sarcoplasmic reticulum (SR) and plasma membranes from canine left ventricle were used to evaluate the presence of the enzyme CDPdiglyceride-inositol transferase in these membranes. (K+,-Ca2+)-ATPase activity, a marker for SR, was 79.2 +/- 5.0 (SE) and 11.2 +/- 2.0 mumol.mg-1.h-1 in SR and plasma membrane preparations, respectively, and (Na+,K+)-ATPase activity, a marker for plasma membranes, was 5.6 +/- 1.2 and 99.2 +/- 8.0 mumol.mg-1.h-1, respectively. Contamination of SR and plasma membrane preparations by mitochondria was estimated to be 2% and 8%, respectively, and by Golgi membranes, 0.9% and 1.8%, respectively. Transferase activity, measured at pH 6.8, was 1.32 +/- 0.04 (SE) and 0.28 +/- 0.04 nmol of [3H]phosphatidylinositol ([3H]PtdIns).mg-1.min-1 in three SR and plasma membrane preparations, respectively. The transferase activity detected in the plasma membrane preparation could be accounted for largely, but not entirely, by contaminating SR membranes. The pH optimum for the SR transferase activity was between 8.0 and 9.0; little or no activity was detectable at pH 6.3 and 5.5, the lowest pH tested. Ca2+ inhibited the enzyme, half-maximal inhibition occurring at about 10 microM Ca2+; removal of the Ca2+ by addition of ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid restored activity. No loss of [3H]PtdIns could be detected when membranes were incubated in the presence or absence of Ca2+. The Ca2+ inhibition of the transferase was noncompetitive with respect to CDP-dipalmitin while that with respect to myo-inositol was slightly noncompetitive at low [Ca2+] and became uncompetitive at higher [Ca2+].(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphatases↗
PubMed1988

A regulation of the level of phosphorylated phospholamban by inhibitor-1 in rat heart preparations in vitro.

Inhibitor-1 following phosphorylation by protein kinase A inhibits phosphoprotein phosphatase-1. We have found that in the rat heart inhibitor-1 is present only in the cytosolic fraction and that its phosphorylation in ventricular slices was increased by isoproterenol but not by isoproterenol and propranolol together. Cardiac microsomal phosphoprotein phosphatase activity, with added phosphorylase a as the substrate, was inhibited 33% by phosphorylated inhibitor-1. Phosphorylated inhibitor-1 decreased the dephosphorylation by exogenous phosphoprotein phosphatase-1 of phospholamban present in the sarcoplasmic reticulum membranes. These results suggest an interaction of cytoplasmic inhibitor-1 with either cytoplasmic or membrane-bound phosphoprotein phosphatase-1 with a subsequent effect on the level of phosphorylated phospholamban and the probable involvement of this interaction in the cardiac response to beta-adrenergic hormones.

Adenosine Triphosphatases↗
PubMed1986

Proteolytic activation of the canine cardiac sarcoplasmic reticulum calcium pump.

Mild trypsin treatment of canine cardiac microsomes consisting largely of sarcoplasmic reticulum vesicles produced a severalfold activation of oxalate-facilitated calcium uptake. The increase in calcium uptake was associated with an increase in ATP hydrolysis. Proteases other than trypsin were also effective although to a lesser degree. Trypsin produced a shift of the Ca2+ concentration dependency curve for calcium uptake toward lower Ca2+ concentrations, which was almost identical with that produced by phosphorylation of microsomes by cyclic AMP dependent protein kinase when the trypsin and the protein kinase were present at maximally activating concentrations. The Hill numbers (+/- SD) of the Ca2+ dependency after treatment of microsomes with trypsin (1.5 +/- 0.1) or protein kinase (1.7 +/- 0.1) were similar and were not significantly different from those for untreated control microsomes (1.6 +/- 0.1 and 1.8 +/- 0.1, respectively). Autoradiograms of sodium dodecyl sulfate-polyacrylamide electrophoretic gels indicate that 32P incorporation into phospholamban (Mr 27.3K) or its presumed monomeric subunit (Mr 5.5K) was markedly reduced when trypsin-treated microsomes were incubated in the presence of cyclic AMP dependent protein kinase and [gamma-32P]ATP compared to control microsomes incubated similarly but pretreated with trypsin inhibitor inactivated trypsin. The activation of calcium uptake by increasing concentrations of trypsin was paralleled by the reduction of phosphorylation of phospholamban. Trypsin treatment of microsomes previously thiophosphorylated in the presence of cyclic AMP dependent protein kinase and [gamma-35S]thio-ATP did not result in a loss of 35S label from phospholamban, which suggests that phosphorylation of phospholamban protects against trypsin attack.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1977

Decrease in calcium transport associated with phosphoprotein phosphatase-catalyzed dephosphorylation of cardiac sarcoplasmic reticulum.

Phosphoprotein phosphatase activity is found in preparations of sarcoplasmic reticulum isolated from canine heart when assayed with either phosphate or phosphorylated sarcoplasmic reticulum as substrate. Phosphoprotein phosphatase-catalyzed dephosphorylation of the 22,000 dalton phosphoprotein of cardiac sarcoplasmic reticulum is stimulated markedly by MnCl2 (5 mM) and to a lesser extent by MgCl2 (5 mM); inorganic phosphate (50 mM) and NaF (25 mM) are inhibitory. Dephosphorylation of this 22,000 dalton phosphoprotein is correlated with a decreased initial rate of calcium transport. The close structural and functional relationship of phosphoprotein phosphatase to the cardiac sarcoplasmic reticulum suggests a possible role of this enzyme in reversing the relaxation-promoting effects of catecholamines on the intact heart.

Animals↗
PubMed1976

Effects of adenosine 3':5'-monophosphate-dependent protein kinase on sarcoplasmic reticulum isolated from cardiac and slow and fast contracting skeletal muscles.

Effects of cyclic adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase were studied in sarcoplasmic reticulum prepared from cardiac and slow and fast (white) skeletal muscle. Cyclic AMP-dependent protein kinase failed to catalyze phosphorylation of fast skeletal muscle microsomes as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cyclic AMP-dependent protein kinase was without effect on calcium uptake by these microsomes. Treatment of cardiac microsomes obtained from dog, cat, rabbit, and guinea pig with cyclic AMP-dependent protein kinase and ATP resulted in phosphorylation of a 22,000-dalton protein component in the amounts of 0.75, 0.25, 0.30, and 0.14 nmol of phosphorus/mg of microsomal protein, respectively. Calcium uptake by cardiac microsomes was stimulated 1.8- to 2.5-fold when microsomes were treated with cyclic AMP-dependent protein kinase. Protein kinases partially purified from bovine heart and rabbit skeletal muscle were both effective in mediating these effects on phosphorylation and calcium transport in dog cardiac sarcoplasmic reticulum. Slow skeletal muscle sarcoplasmic reticulum also contains a protein with a molecular weight of approximately 22,000 that can be phosphorylated by protein kinase. Phosphorylation of this component ranged from 0.005 to 0.016 nmol of phosphorous/mg of microsomal protein in dog biceps femoris. A statistically significant increase in calcium uptake by these membranes was produced by the protein kinase. Increases in protein kinase-catalyzed phosphorylation of a low molecular weight microsomal component and in calcium transport by sarcoplasmic reticulum of cardiac and slow skeletal muscle may be related to the relaxation-promoting effects of epinephrine seen in these types of muscle. Conversely, the absence of a relaxation-promoting effect of epinephrine in fast skeletal muscle may be associated with the lack of effect of cyclic AMP and protein kinase on calcium transport by the sarcoplasmic reticulum of this type of muscle.

Animals↗
PubMed1976

Correlation between protein kinase-mediated stimulation of calcium transport by cardiac sarcoplasmic reticulum and phosphorylation of a 22000 dalton protein.

Increases in protein kinase-catalyzed phosphorylation of a 22000 dalton protein correlated closely with increases in phosphate-facilitated calcium transport measured concurrently in canine cardiac sarcoplasmic reticulum under similar conditions in the presence of varying concentrations of bovine cardiac protein kinase. A correlation coefficient of 0.93 and a P value of less than 0.001 were obtained. Protein kinase-catalyzed phosphorylation of the 22000 dalton microsomal protein may mediate the abbreviation of systole seen in the mammalian heart in response to inotropic agents like catecholamines.

Animals↗
PubMed1976

Biochemical properties of cardiac sarcolemma: adenylate cyclase and (Na++K+)-activated ATPase.

Morphologically intact plasma membranes from guinea pig ventricles were obtained by exposing isolated cell segments to osmotic shock, followed by extraction of actomyosin in 1 M KC1. These preparations contained approximately 1/6 of the protein and 5-10 percent of the mitochondrial markers present in the original cell preparation. Both adenylate cyclase and (Na++K+)-activated ATPase activities were enriched 3-4 fold. The receptor for epinephrine stimulation of adenylate cyclase was retained. The "basal" ATPase activity of 5-6 mumoles of Pi/mg/hr, measured in 120 mM NaC1 or KC1, was approximately doubled in 100 mM NaC1+20 mM KC1. This increment, the (Na++K+)-activated ATPase, was abolished by 10(-5) M ouabain, the Ki for ouabain being approximately 3x10(-7) M. Adenylate cyclase, which had a basal activity of approximately 0.33 nmole of cyclic AMP produced/min/mg of protein, was significantly stimulated by both l-epinephrine and NaF. Half-maximal stimulation was seen at approximately 5x10(-6) M l-epinephrine. Increasing Ca2+ in the range between 10(-7) and 10(-3) M inhibited basal, l-epinephrine-, and NaF-stimulated adenylate cyclase activities. Basal rates of cyclic AMP production were more sensitive to Ca2+ than was l-epinephrine-stimulated adenylate cyclase activity, so that l-epinephrine stimulation was increased from approximately 60 percent in 0.5 mM ethylene glycol bis (beta-aminoethyl ether) N,N'-tetraacetic acid to approximately 150 percent in 10(-7)M Ca2+ and 400 percent in 10(-5) M Ca2+. The inhibitory effect of Ca2+ on adenylate cyclase activity may represent a negative feedback mechanism by which eelevation of intracellular Ca2+ concentration lowers cellular levels of cyclic AMP and thus reduces Ca2+ influx into the myocardium.

Adenosine Triphosphatases↗
PubMed1976

Regulation of calcium transport in cardiac sarcoplasmic reticulum by cyclic AMP-dependent protein kinase.

A manyfold increase in phosphorylation of cardiac sarcoplasmic reticulum (SR) was seen when SR was incubated in the presence of a bovine cardiac cyclic AMP-dependent protein kinase and cyclic AMP. This phosphoprotein had stability characteristics of a phosphoester in which the phosphate is incorporated largely into serine, and its formation did not required calcium ions, unlike the formation of acyl phosphoprotein intermediate of calcium-transport ATPase which is present within the same membrane. When examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the protein kinase-catalyzed phosphorylation occurred at a 22,000-dalton component of the cardiac sarcoplasmic reticulum. This 22,000-dalton protein has been named "phospholamban" (lambda alpha mu beta alpha nu epsilon iota nu = to receive), based on its ability to receive phosphate from ATP. Phosphorylation of phospholamban by cyclic AMP-dependent protein kinase was associated with the stimulation of calcium transport by the cardiac sarcoplasmic reticulum. This stimulation was accompanied by an increase in the calcium-activated ATPase activity, indicating that the overall rate of calcium transport rather than its efficiency is enhanced by protein kinase. The 22,000-dalton phopholamban was susceptible to trypsin. Brief digestion with trypsin in the presence of 1 M sucrose prevented subsequent phosphorylation of phospholamban, while leaving the calcium pump apparently intact. Incubation of trypsin-treated sarcoplasmic reticulum with cyclic AMP-depentent protein kinase did not result in the stimulation of calcium transport. These results may suggest that phospholamban is a modulator of the calcium pump of the cardiac sarcoplasmic reticulum.

Animals↗
PubMed1975

Phosphorylation of a 22,000-dalton component of the cardiac sarcoplasmic reticulum by adenosine 3':5'-monophosphate-dependent protein kinase.

Cardiac microsomes were incubated with [gamma-32P]ATP and a cardiac adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase in the presence of ethylene glycol bis(bets-aminoethyl ether)-N,N'-tetraacetic acid. After solubilization in sodium dodecyl sulfate and fractionation by polyacrylamide gel electrophoresis, a single microsomal protein component of approximately 22,000 daltons was found to bind most of the 32P label. The 32P labeling of this component increased several fold when NaF was included in the incubation medium. No other component of cardiac microsomes, including sarcoplasmic reticulum ATPase protein, contained significant amounts of 32P label. This 22,000-dalton phosphoprotein formed by cyclic AMP-dependent protein kinase had stability characteristics of a phosphoester rather than an acyl phosphate. Washing of microsomes with buffered KCl did not decrease the amount of 32P labeling to the 22,000-dalton protein, suggesting that this protein is associated with the membranes of sarcoplasmic reticulum rather than being a contaminant from other soluble proteins. The 22,000-dalton protein was susceptible to trypsin. Brief digestion with trypsin in the presence of 1 M sucrose did not significantly affect microsomal calcium transport activity, but prevented both subsequent phosphorylation of the 22,000-dalton protein and stimulation of calcium uptake by cyclic AMP-dependent protein kinase, suggesting that this protein is a modulator of the calcium pump. These results are consistent with previous findings (Kirchberger, M.A., Tada, M., and Katz, A.M. (1974) J. Biol. Chem. 249, 6166-6173; Tada, M., Kirchberger, M.A., Repke, D.I., and Katz, A.M. (1974) J. Biol. Chem. 249, 6174-6180) that cyclic AMP-dependent protein kinase-catalyzed phosphorylation is associated with stimulation of calcium transport in the cardiac sarcoplasmic reticulum, and further indicate that this phosphorylation occurs at a component of low mass (22,000 daltons) of the cardiac sarcoplasmic reticulum which, while separable from the calcium transport ATPase protein (100,000 daltons) by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, has the ability to regulate calcium transport by the cardiac sarcoplasmic reticulum.

Animals↗
PubMed1975

Control of cardiac sarcolemmal adenylate cyclase and sodium, potassium-activated adenosinetriphosphatase activities.

A plasma membrane preparation purified from guinea pig ventricles without the use of high concentrations of detergents or structure-disrupting salts was used to compare the mechanisms of controlling sodium, potassium-activated adenosinetriphosphatase (Na, K-ATPase) and adenylate cyclase activities. The basal ATPase activity of 4-6 mu moles P1/hour mg-1 protein, measured in 120 mM NaC1 or KC1, was approximately doubled in 100 mM NaC1 plus 20 mM KC1. This increment, the Na, K-ATPase, was abolished by 10-5M ouabain, the K1 for ouabain being approximately 3 X 10-7M. 1-Epinephrine had no effect on Na, K-ATPase, but NaF was inhibitory. Adenylate cyclase, which had a basal activity of approximately 50% by NaC1 or KC1 alone at concentrations up to 0.2M. There was no additional stimulation of adenylate cyclase activity when na+ K+ included together. Both 1-epinephrine and NaF cause significant stimulation of adenylate cyclase, but neither basal nor activated cyclic AMP PRODUCTION WAS INFLUENCED BY OUABAIN. Half-maximal stimulation was seen at approximately 5 X 10-6M 1-epinephrine. Both the catecholamine and NaF increased the V-max ofcardiac plasma membrane adenylate cyclase without significantly influencing Km. Increasing Ca2+ in the range between 10-7 and 10-3M inhibited basal, 1-epinephrine-stimulated, and NaF-stimulated activities. Basal rates of cyclic AMP production were more sensitive to Ca2+ than was 1-epinephrine stimulation was increased from approximately 60% in 0.5 mM EGTA to approximately 150% in 10-7M Ca2+ and 400% in 10-5M Ca2+. The inhibitory effect of Ca2+ on adenylate cyclase activity may represent a negative feed back mechanism by which elevation of intracellular Ca2+ concentration lowers cellular levels of cyclic AMP and thus reduces Ca2+ influx into the myocardium.

Adenosine Triphosphatases↗
PubMed1975

Control of calcium transport in the myocardium by the cyclic AMP-Protein kinase system.

At least three mechanical changes characterize the response of cardiac muscle to agents that enhance cyclic AMP production. In common with other inotropic interventions, tension is augmented and the rate of tension rise is increased. The third response, acceleration of the rate of relaxation, is characteristic of the actions of beta-adrenergic agonists. These mechanical effects can be attributed to changes in (1) the amount of Ca2+ released during systole, (2) the rate of Ca2+ release at the onset of systole, and (3) the rate at which Ca2+ is reaccumulated by the sarcoplasmic reticulum at the end of systole. The ability of cyclic AMP-dependent protein kinases to phosphorylate the cardiac sarcoplasmic reticulum in vitro parallels stimulation of both Ca2+ transport and Ca2+-activated ATPase. The phosphoprotein formed in the presence of cyclic AMP and protein kinase has the chemical characteristics of a phosphoester, contains mostly phosphoserine, and has an electrophoretic mobility in SDS polyacrylamide gels that corresponds to a protein of 22,000 daltons. This 22,000-dalton protein, tentatively named phospholamban, thus differs from the acyl phosphooprotein formed by the Ca2+-transport ATPase, which as an apparent molecular weight of 90,000 to 100,000 daltons. Phospholamban has not been found in fast skeletal muscle, nor is Ca2+ transport accelerated by cyclic AMP and protein kinase in sarcoplasmic reticulum from these muslces which do not respond to beta-adrenergic agonists with accelerated relaxation. It thus appears likely that phosphorylation of phospholamban correlates both with an increased rate of Ca2+ transport by cardiac sarcoplasmic reticulum in vitro and accelerated relaxation in the intact myocardium. Preliminary findings are consistent with the view that phosphorylation of phospholamban may be related to other actions on Ca2+ fluxes brought about by agents which activate adenylate cyclase in the myocardium, but these interpretations must remain speculative pending more definitive studies.

Adenosine Triphosphatases↗
PubMed1975

Phosphoprotein phosphatase-catalyzed dephosphorylation of the 22,000 dalton phosphoprotein of cardiac sarcoplasmic reticulum.

The present study demonstrated the presence within the myocardium of phosphoprotein phosphatase activity which can account for dephosphorylation of a 22,000 dalton phosphoprotein of cardiac sarcoplasmic reticulum that has been associated with the stimulatory effects of adenosine 3':5'-monophosphate (cyclic AMP)-dependent protein kinase on calcium transport (Tada, M., Kirchberger, M. A., and Katz, A. M. (1975) J. Biol. Chem. 250:2640-2647). Dog cardiac microsomes, consisting mainly of fragmented sarcomplasmic reticulum, were phosphorylated by incubation with cyclic AMP-dependent protein kinase and [gamma-32P]ATP, and subsequently washed with trichloroacetic acid or buffered KCl. Phosphorylated microsomes contained approximately 1 nmole of 32P bound per mg of microsomal protein, 32P labeling occurring almost exclusively at the 22,000 dalton component. Soluble phosphoprotein phosphatases, isolated from the cytosol, catalyzed dephosphorylation of 32P-labeled microsomes. The existence of a phosphoprotein phosphatase that is associated with the microsomes was demonstrated by the ability of the microsomes to dephosphorylate 32P-histone. This membrane-associated phosphatase activity can also account for a rapid decrease in the amount of 32P-labeling of the 22,000 dalton protein. The dephosphorylation of the phosphorylated 22,000 dalton protein by phosphoprotein phosphatase satisfies an important requirement for the phosphorylation of the 22,000 dalton protein to serve a physiological role, namely, its reversibility.

Animals↗