Hormonal Regulation of Cyclic‐AMP‐Dependent Protein Kinase of Rat Diaphragm by Epinephrine and Insulin

Walaas, Otto; Walaas, Eva; Grønnerød, Ole

doi:10.1111/j.1432-1033.1973.tb03215.x

Cited by 55 publications

(16 citation statements)

References 37 publications

(8 reference statements)

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“…by a protein kinase inhibitor). Similar results have been reported by Walaas et al (1973), who found that cyclic AMP-independent protein kinase formed during incubation of muscle tissue was mainly converted into an inactive complex in muscle extracts. The cyclic AMP-dependent protein kinase, on the other hand, was stable and could be quantitatively recovered after fractionation and purification procedures.…”

Section: Discussionsupporting

confidence: 79%

Protein kinase activity in rat testis interstitial tissue. Effect of luteinizing hormone and other factors

Cooke¹,

Kemp²

1976

Biochemical Journal

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Protein kinase:activity was determined in subcellular fractions of-rat testis interstitial tissue after-incubation ofthe-intact tissue with LH (luteinizing ¶hormone) in vitro. Various factors that might have changed the activity of this .enzyme during preparation of the fractions beforeassay were also investigated. The following results were obtained. 1.LLH and 34sobutyl-b 1methylxanthine (a phosphodiesterase inhibitor) added together-during incubation of the interstitial tissue,caused a twofold increasein the protein kinase-activity in :the total tissue homogenate and subcellular fractions (12000gx5min pellet and 0 5O0fgx60min supernatant and pellet). 2. A decrease of approx. 40% in -the total amount of proteinkinaserecovered in the solublefraction (1O5Q00gsupernatant}occurred in tissue incubated with -LH and 3-isobutyl-1-methylxanthine when compared with the controls. No change in total activity was found in the other fractions. 3. LH Sand 3-isobutyl4ln-methylxanthine caused;an increase in cyclic AMP concentration in the soluble fraction (from, 30±6 to 450±+4prnio1/mg of protein, -means±S.E.M., -n=4), but there -waslittle orno inceaseinthe paitiqulate.fractions [from 9± to 13 + &pmol/mg ofprotein (n =3) and -from,6±2)to 23+1l1pmol/mg of protein,(n =-3) in thle 12000gand-.105000g -pellets respectively]. 4. Addition of 3-isobutyl.l-methylxanthine alone had little effect -on protein kinase activity or cyclic-AMP concentrations. 5. Little or no protein kinase .activity could be-demonstrated in subcellular particulate fractions-unless Triton X-I00 was added; the effect of this detergent was shown.to;be at least partly due to the inhibition -of adenosine triphosphatase activity. 6. In the presence of Triton X-100 approx. 57% of the total protein Ekinase activity in the homogenate was found in the 105 OOOg supernatant compared with 11 %in-the 1-OSOOg pellet and 32% in the 4200g-pellet. 7. In contrast mith adipose-tissue protein kinase [Corbin et al. (1973)-J. Biol. Chem. 248, 1813-1821 the.relative amounts -of cyclic AMP-independent and -dependent enzyme -were -not affected by dilution of the interstitial-tissue fractions. NaCl (0.5M) decreased the estimated total amount of protein kinase activity.

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Section: Discussionsupporting

confidence: 79%

Protein kinase activity in rat testis interstitial tissue. Effect of luteinizing hormone and other factors

Cooke¹,

Kemp²

1976

Biochemical Journal

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“…Insulin inhibits hepatic cAMP-dependent protein kinase in the absence of any changes in cyclic adenine nucleotide concentrations (4)(5)(6). A similar inhibition ofprotein kinase activity has been observed in diaphragm (7) and skeletal muscle (8); however, the mechanism of this response has remained obscure.…”

supporting

confidence: 54%

Insulin inhibition of hepatic cAMP-dependent protein kinase: decreased affinity of protein kinase for cAMP and possible differential regulation of intrachain sites 1 and 2.

Gabbay¹,

Lardy²

1987

Proc. Natl. Acad. Sci. U.S.A.

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In hepatocytes stimulated with 8-bromocAMP, insulin decreases the affinity of the cAMP-dependent protein kinase for cAMP, shifting the Ka without affecting the V.,, activity. This occurs under conditions where cyclic adenine nucleotide concentrations are unchanged. We report here that glycogenolysis stimulated by 8-(4-chlorophenylthio)-cAMP, an analog with 100 times tighter affinit than cAMP for the protein kinase regulatory subunit, was only slightly antagonized by insulin. The tight binding of this analog appears to overcome the protein kinase affinity change induced by insulin. The relative importance of the two intrachain cAMP binding sites of the cAMP-dependent protein kinase regulatory subunit was investigated by using analogs with relative selectivity for each site. Analogs exhibiting preferential binding to site 2Dwere far less sensitive to insulin antagonism than were analogs binding preferentially at site 1 and less well at site 2. No other property of these analogs, including the rate of hydrolysis by phosphodiesterase, the IC50 for phosphodiesterase, the Ka for protein kinase, or the type I versus type II kinase specificity, could account for the ability of insulin to antagonize glycogenolysis stimulated by these analogs. These data indicate that insulin may act to decrease the affinity of protein kinases for cAMP through a possible regulation of intrachain site 2 binding.Glucagon, by increasing intracellular cAMP levels, activates cAMP-dependent protein kinases. Its counterregulatory hormone, insulin, can antagonize these responses through several mechanisms (for a review, see ref. 1). Insulin stimulates hepatic cAMP phosphodiesterase to decrease cAMP concentrations (2, 3); however, cAMP destruction is not required to terminate the glucagon signal (4). Insulin inhibits hepatic cAMP-dependent protein kinase in the absence of any changes in cyclic adenine nucleotide concentrations (4-6). A similar inhibition ofprotein kinase activity has been observed in diaphragm (7) and skeletal muscle (8); however, the mechanism of this response has remained obscure.In recent years, many analogs of cAMP have been developed with differing specificities towards protein kinase (9, 10). Corbin and coworkers (11,12) have discovered that the regulatory subunit of the cAMP-dependent protein kinase contains two intrachain cAMP binding domains? termed site 1 and site 2, based on their sensitivity to various cAMP analogs. Both binding sites appear to be involved in protein kinase activation (13,14). The differing specificities of these cAMP analogs permit the examination of protein kinase regulation in intact cells. In perfused heart, insulin decreases[3H]cIMP binding, which is specific for intrachain site 2, suggesting the possible regulation of this binding site on protein kinase (15).Here we demonstrate that, in liver, insulin can decrease the affinity of cAMP-dependent protein kinase for cAMP and indicate a possible role for intrachain site 2 binding based on the specificity of insulin antagonism of several cAMP ...

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“…Reserpine causes an immediate increase of the cAMP/cGMP concentration ratio (11,12) and a delayed induction of monooxygenase activity in adrenal medulla (3). It was reported by Otten et al (13) that when reserpine (16 umol/kg intraperitoneally) was given 30 min after an injection of propranolol (40 umol/kg intraperitoneally), the medullary cAMP content failed to increase; however, the induction of adrenal tyrosine monooxygenase remained unimpaired (13). We have repeated the experiment shows that the two slopes are equal.…”

Section: Resultsmentioning

confidence: 99%

“…10 Il of 0.1 M Mg acetate buffer (pH 6.0), 40 ,l of 0.5 M Na acetate buffer (pH 6.0), 10 ,ul of 0.3 M NaF, 10 jAl of 65 mM aminophylline, 20,A of calf histone mixture (2 mg/ml), 30 ,ul of H20, and 10 ,ul of cAMP or H20. The reaction was initiated by adding 10 ,ul of 0.5 mM [32P]ATP (specific activity, 100 ,Ci/,umol).…”

mentioning

confidence: 99%

Protein kinase activation as an early event in the trans-synaptic induction of tyrosine 3-monooxygenase in adrenal medulla.

Guidotti¹,

Kurosawa²,

Chuang³

et al. 1975

Proc. Natl. Acad. Sci. U.S.A.

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An increase of cAMP/cGMP concentration ratio is the earliest stimulus-coupled biochemical change that has been measured in the adrenal medulla during the trans-synaptic induction of tyrosine 3-monooxygenase [EC 1.14.16.2; L-tyrosine, tetrahydropteridine: oxygen oxidoreductase (3-hydroxylating)]. In adrenal medulla of rats receiving reserpine alone (16 Amol/kg intraperitoneally) or reserpine and propranolol (40 Amol/kg intraperitoneally 30 min before reserpine), or exposed to 40 for 4 hr, the extent and duration of the increase of the cAMP/cGMP concentration ratio exceeds the critical value that is required to activate the protein kinases (EC 2.7.1.37; ATP:protein phosphotransferase). Gel filtration experiments indicate that during this activation, the catalytic subunit of the protein kinase (low-molecular-weight enzyme) is released from the holoenzyme. The activation of protein kinase lasts longer than the increase in the cAMP/cGMP concentration ratio and appears to be an obligatory early event that mediates the increase of tyrosine monooxygenase synthesis. The trans-synaptic induction of the monooxygenase in adrenal medulla appears to be due to an increased synthesis of the enzyme; the rate for monooxygenase degradation is proportional to the number of enzyme molecules that are present at various stages of the induction process.

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Hormonal Regulation of Cyclic‐AMP‐Dependent Protein Kinase of Rat Diaphragm by Epinephrine and Insulin

Cited by 55 publications

References 37 publications

Protein kinase activity in rat testis interstitial tissue. Effect of luteinizing hormone and other factors

Protein kinase activity in rat testis interstitial tissue. Effect of luteinizing hormone and other factors

Insulin inhibition of hepatic cAMP-dependent protein kinase: decreased affinity of protein kinase for cAMP and possible differential regulation of intrachain sites 1 and 2.

Protein kinase activation as an early event in the trans-synaptic induction of tyrosine 3-monooxygenase in adrenal medulla.

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