Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Addition of adenosine 3':5'-monophosphate (cAMP) to high speed supernatant preparations obtained from rat brain caused a 3- to 4-fold increase in tyrosine 3-monooxygenase (tyrosine hydroxylase) activity. The tyrosine 3-monooxygenase remained in an activated state upon removal of the cAMP by passing the enzyme through a Sephadex G-25 column. Substances which inhibit cAMP-dependent protein kinase, namely, EDTA, ADP, and adenosine, and protein kinase modulator, each antagonized the activation of tyrosine 3-monooxygenase produced by cAMP. Furthermore, addition of partially purified brain cAMP-dependent protein kinase caused a several-fold increase in tyrosin 3-monooxygenase activity. The activation of tyrosine 3-monooxygenase by added cAMP and protein kinase required the presence of ATP and Mg-2+. These data suggests that the cAMP activation of tyrosine 3-monooxygenase may be mediated by a cAMP-dependent protein kinase.
 ...
PMID:Evidence for involvement of protein kinase in the activation by adenosine 3':5'-monophosphate of brain tyrosine 3-monooxygenase. 23 70

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 mumol/kg intraperitoneally) or reserpine and propranolol (40 mumol/kg intraperitoneally 30 min before reserpine), or exposed to 4 degrees 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.
 ...
PMID:Protein kinase activation as an early event in the trans-synaptic induction of tyrosine 3-monooxygenase in adrenal medulla. 23 57

Protein phosphorylation is a ubiquitous form of posttranslational protein modification in mammalian cells which often serves to regulate protein function. Insulin alters the activity of a number of enzymes known to be regulated via phosphorylation. With the premise that altered protein phosphorylation might be an obligatory intermediate step in insulin action, we have examined the effects of insulin on the phosphorylation of the major phosphopeptides in adipocytes and hepatocytes. Insulin affects overall protein phosphorylation in two ways: 1) Insulin selectively stimulates the phosphorylation of a major peptide in adipose tissue (MW 123,000) and liver (MW 46,000) through a mechanism independent of cAMP and the cAMP-dependent protein kinase. Net dephosphorylation is not observed with insulin as the sole hormone. 2) Insulin antagonizes cAMP-directed protein phosphorylation. The mechanism of insulin-stimulated phosphorylation and the possible role of this phenomenon in overall insulin action is discussed.
 ...
PMID:Insulin and the phosphorylation of intracellular proteins. 39 36

DEAE-cellulose chromatography of the 105,000 X g supernatant fraction (cytosol) obtained from popped estrous rabbit follicles revealed the presence of a single form of cAMP-dependent protein kinase, designated protein kinase 3. The iv injection of an ovulatory dose of hCG to estrous rabbits promoted the appearance of a second, transient peak of cytosol cAMP-dependent protein kinase, protein kinase 1. Protein kinase 1 was detected within 10 min of hCG administration but had regressed to undetectable levels by 24 h in corpora lutea (CL) of pseudopregnancy and by 72 h in CL of pregnancy. Ovulation and subsequent CL formation were accompanied by the appearance of a third form of cAMP-dependent protein kinase, designated protein kinase 2. Protein kinase 2 was present within 2 h after hCG administration and persisted as a major form of cytosol cAMP-dependent protein kinase throughout the life span of CL. All three forms of protein kinase were inhibited by the heat-stable protein kinase inhibitor from rabbit skeletal muscle, possessed cAMP-binding activity, and were markedly stimulated by 10(-7) M cAMP. The activity of protein kinase 3 in CL of pregnancy, in corpora albicantia, and in interstitial tissue was markedly greater than that in follicles or in CL of pseudopregnancy, while the activity of protein kinase 2 remained relatively constant throughout the luteal life span. The iv injection of a luteolytic dose of hCG to 4-day pseudopregnant rabbits promoted no alterations of the protein kinase elution profile upon DEAE-cellulose chromatography of the luteal cytosol obtained 10 min to 3 days post-hCG injection. However, with dedifferentiation of corpora albicantia into interstitial tissue, the cAMP dependency of protein kinase 2 was reduced. The results indicate that the enzymatic activity and multiplicity of cAMP-dependent protein kinases in the cytosol of ovarian structures are subject to regulation by LH (hCG) and depend upon the various reproductive stages of the rabbit.
 ...
PMID:Rabbit ovarian protein kinases. II. Effect of an ovulatory dose of human chorionic gonadotropin or luteinizing hormone on the multiplicity of follicular and luteal protein kinases. 57 Apr 95

Whole homogenates prepared from tissue previously exposed to epinephrine displayed a 3-fold increased rate of lipolysis of endogenous substrate. When the aqueous infranatant phase of such homogenates was collected by centrifugation and assayed against exogenous triolein emulsions, no hormone effect could be demonstrated. Treatment of such infranatants with cAMP-dependent protein kinase prepared from muscle increased their lipase activity against exogenous triolein by 80%. Employing [3H]triolein emulsions as exogenous substrate, rates of lipolysis of both endogenous and exogenous glycerides were measured simultaneously in whole tissue homogenates. Prior treatment of the tissue with epinephrine increased the rate of lipolysis of endogenous glycerides an average of 3-fold but had no effect on the hydrolysis of exogenous triolein. By contrast, treatment of whole homogenates with protein kinase accelerated lipolysis of exogenous triolein without altering the rate of hydrolysis of endogenous glycerides. The data suggest that a second pathway of lipolysis activation occurs in response to epinephrine in addition to that involving a cAMP-mediated increase in the state of phosphorylation of the hormone-sensitive lipase.
 ...
PMID:Evidence for a dual mechanism of lipolysis activation by epinephrine in rat adipose tissue. 63 89

The effects of vasopressin and some of its inhibitors on the extent of MT polymerization (assembly) were studied in renal medullary slices by means of temperature-dependent polymerization-depolymerization procedure to determine the relative ratio of free (unpolymerized) tubulin to assembled MT's. Assembled MT's were stabilized in a medium containing high concentrations of glycerol and DMSO. Tubulin was assessed indirectly by the [3H]-CLC-binding assay. Incubation of slices at temperatures higher than 20 degree C promoted MT polymerization. Although vasopressin markedly increased the tissue levels of cAMP and activated in situ cAMP-dependent protein kinase, it did not change the extent of MT polymerization. On the other hand, VBL and to a lesser degree lithium chloride inhibited the rate of MT assembly. This finding suggests that VBL and lithium, which are known to inhibit the antidiuretic effect of vasopressin in vivo, may exert at least part of their inhibitory effect by interfering with MT assembly in the renal medulla. Present results thus are consistent with the view that vasopressin does not influence the extent of cytoplasmic MT polymerization in spite of the increase in tissue cAMP level and activation of protein kinase but that inact MT's are required for the cellular action of vasopressin.
 ...
PMID:Microtubule assembly in renal medullary slices: effects of vasopressin, vinblastine, and lithium. 68 12

Under conditions favoring its autocatalytic reaction, phosphorylase kinase may be activated and phosphorylated in 2-(N-morpholino)ethanesulfonate (Mes) buffer to a much higher level than in beta-glycerophosphate buffer. The fact that the reaction is autocatalytic is supported by several observations: (a) the progress curve of the reaction exhibits a pronounced lag phase, (b) the reaction is strongly inhibited by ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetate, which inhibits phosphorylase kinase, (c) the pH profile of the reaction resembles that of the phosphorylase b to a reaction as catalyzed by nonactivated phosphorylase kinase, and (d) the reaction is not significantly affected by adenosine 3':5'-monophosphate (cAMP) nor by the heat-stable protein inhibitor of cAMP-dependent protein kinases. When fully autoactivated, phosphorylase kinase possesses an activity that is 100% higher than that of the protein kinase-activated form. The results suggest that autophosphorylation of phosphorylase kinase may be an important regulatory mechanism. The autocatalytic reaction involves phosphorylation of the two larger subunits of phosphorylase kinase, i.e. subunits A and B, with a combined total of 7 to 9 phosphates incorporated per mol of enzyme. Although the cAMP-dependent protein kinase also catalyzes the phosphorylation of subunits A and B, the two mechanisms of phosphorylation appear to involve different sites. Prior phosphorylation of phosphorylase kinase by the protein kinase has little effect on the level of autophosphorylation. Thus activation of phosphorylase kinase may be brought about by phosphorylation of the enzyme at different sites.
 ...
PMID:A study on the autoactivation of rabbit muscle phosphorylase kinase. 94 93

In order to directly evaluate the role of the cAMP-dependent protein kinase (PKA) catalytic (C) subunit in T-cell receptor- (TCR) triggered cytotoxic T-lymphocytes (CTL) effector functions, cells were studied after pretreatment with antisense oligomers complementary to mRNA for the C alpha or C beta subunits. C alpha subunit is shown to be predominantly expressed in CTL. In some experiments the pretreatment of the CTL with the C alpha antisense, but not with the control or C beta antisense oligomers, resulted in the inhibition of cAMP-independent PKA activity without significantly affecting the level of total cAMP-inducible PKA activity. In parallel assays, CTL which were pretreated with the C alpha antisense oligomer had enhanced antigen-bearing target cell-triggered-, anti-TCR monoclonal antibody-triggered-, and phorbol 12-myristate 13-acetate/A23187-triggered exocytosis of granules, as well as enhanced antigen-specific cytotoxicity. In contrast, the TCR-triggered gamma-interferon mRNA expression and gamma-interferon secretion were inhibited in C alpha antisense-pretreated CTL. These results suggest that the C alpha subunit of PKA may have a dual role in regulation of T-lymphocytes effector functions: (i) it may down-regulate TCR-triggered protein-synthesis independent responses such as cytotoxicity and exocytosis, thereby counteracting TCR-triggered activation even in the absence of the second messenger, cAMP, and (ii) the C alpha subunit activity is likely to be required for the nuclear and/or cytoplasmic events in CTL's activation involved in lymphokine synthesis and secretion.
 ...
PMID:The dual role of the cAMP-dependent protein kinase C alpha subunit in T-cell receptor-triggered T-lymphocytes effector functions. 128 Nov 54

The effect of a cAMP-dependent secretogogue (VIP) on the phosphorylation of an endogenous, membrane-bound protein (pp170) was assessed in an intact cell preparation from the avian salt gland. The addition of VIP, in the presence of 100 microM isobutylmethylxanthine, resulted in a concentration-dependent increase in phosphorylation of pp170. This effect was rapid and transient with a 3-5-fold increase in phosphorylation occurring 1 min after the addition of VIP. Under similar incubation conditions, VIP stimulated a 4.6-fold increase in cAMP accumulation that paralleled phosphorylation. Exposure of cells to either forskolin or 8-Br-cAMP resulted in a 5-8-fold increase in the phosphorylation of pp170. The effect of forskolin was dose dependent with an EC50 similar to that for stimulation of secretion (35 nM). These results implicate an involvement for a cAMP-dependent protein kinase in the phosphorylation of pp170. The identity of pp170 was assessed utilizing a monoclonal antibody (Q3) directed against pp170. Q3 recognized a single 170-kDa band on Western blots of salt gland membrane protein. Immunoprecipitation of pp170 from salt gland cells resulted in the selective extraction of a single protein whose phosphorylation state was increased approximately 5-fold in response to carbachol or VIP. The identity of pp170 was established using two criteria. First, Q3 recognized affinity-purified Na:K:Cl cotransporter preparations from shark rectal gland membranes. Second, pp170 was selectively immunoprecipitated by monoclonal antibodies (J3, J4, and J7) that recognize different epitopes of the shark transport protein. These results suggest that pp170 is homologous to the shark rectal gland Na-K-Cl cotransporter, and thus the proteins may be functionally similar.
 ...
PMID:The Na-K-Cl cotransporter of avian salt gland. Phosphorylation in response to cAMP-dependent and calcium-dependent secretogogues. 128 Nov 59

The enzymes cAMP-dependent protein kinase (PKA) and protein kinase C (PKC) regulate the activity of cardiac ion channel proteins. In this study the whole-cell arrangement of the patch clamp technique was used to examine the effect of NaI on PKA-stimulated Cl- and Ca2+ channels in isolated guinea pig ventricular myocytes. Cl- currents (ICl) activated either by the beta-adrenergic agonist isoproterenol or the membrane-soluble cAMP analogue, 8-chlorphenylthio (8-CPT) cAMP, were greatly reduced in amplitude after substitution of an external solution containing 140 mM NaCl with a solution containing 140 mM NaI. This reduction was accompanied by a shift of -7 mV in the reversal potential (Erev) for ICl and could be reversed upon return to the NaCl external solution. Inhibition of ICl by NaI occurred in a concentration-dependent manner and was more pronounced for inward ICl (IC50 = 19 mM at -60 mV) than for outward ICl (IC50 = 60 mM at +60 mV). In contrast to ICl activated by PKA, ICl activated by PKC was slightly augmented in the presence of NaI and the Erev was found to shift by -15 mV. Based on these data, the relative permeability of I- to Cl- (PI/PCl) for this channel was calculated to be 1.79. NaI produced no change in the amplitude of inward calcium currents (ICa) recorded under basal conditions, but strongly inhibited ICa augmented by isoproterenol and 8-CPT cAMP, and during dialysis of cells with the catalytic subunit of PKA (CS). The in vitro incorporation of [gamma-32P]ATP into histone IIA and Kemptide, measured in the presence of PKA and cAMP, was not significantly different in assay mixtures containing salts of Cl- and I-. However, the ability of isoproterenol to augment basal ICa in whole-cell experiments was attenuated when experiments were carried out entirely in NaI external solution. Thus, the reduction in ICl and ICa observed in this study may result from a direct effect of I- on the phosphorylation/dephosphorylation of cardiac ion channel proteins or associated regulatory proteins.
 ...
PMID:Inhibition of heart calcium and chloride currents by sodium iodide. Specific attenuation in cAMP-dependent protein kinase-mediated regulation. 128 46


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>