Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Na/K/2Cl cotransport system in the avian erythrocyte can be activated by agents that raise intracellular cAMP suggesting the involvement of cAMP-dependent protein kinase (cAMP-PK) in its regulation. Another group of stimuli including fluoride and hypertonicity stimulate cotransport via cAMP-independent means. To further investigate the role of phosphorylation in these processes, we examined the effects of protein kinase inhibitors of 8 (p-Cl-phenylthio)-cAMP (cpt-cAMP), fluoride and hypertonic activation of cotransport in duck red cells, and [3H]bumetanide binding to isolated membranes. Preincubation of cells with the kinase inhibitors K-252a (Ki approximately 1.6 microM) and H-9 (Ki approximately 100 microM) blocked cpt-cAMP activation of bumetanide-sensitive 86Rb influx and bumetanide binding. These inhibitors also led to a rapid deactivation of cotransport and decrease in bumetanide binding when added to cells maximally stimulated by cpt-cAMP. K-252a and H-9 inhibited cotransport activation by cAMP-independent stimuli, but 10-fold higher concentrations were required, implying the involvement of a cAMP-independent phosphorylation process in the mechanism of action of these agents. Removal of stimuli that elevate cAMP leads to a rapid reversal of cotransport indicating the presence of active protein phosphatases in these cells. The protein phosphatase inhibitor okadaic acid (OA, EC50: 630 nM) stimulated both Na/K/2Cl cotransport and bumetanide binding to membranes. As with fluoride and hypertonic stimulation, the OA effect was inhibited only at relatively high concentrations of K-252a. Phosphorylation of the membrane skeletal protein goblin (Mr 230,000) at specific cAMP-dependent sites was used as an in situ marker for the state of activation of cAMP-PK. Goblin phosphorylation at these sites was increased by norepinephrine and cpt-cAMP and rapidly reversed by K-252a and H-9, confirming that both inhibitors do block cAMP-PK activity. While OA markedly increased overall phosphorylation of many erythrocyte membrane proteins, including goblin, it did not affect goblin phosphorylation at specific cAMP-dependent sites. These results implicate a cAMP-independent protein kinase in the mediation of the OA effect on cotransport and bumetanide binding. The bumetanide-binding component of the avian erythrocyte cotransporter, an Mr approximately 150,000 protein that can be photolabeled with the bumetanide analog [3H]4-benzoyl-5-sulfamoyl-3-(3-thenyloxy)-benzoic acid was found to be a phosphoprotein. These results strongly support the hypothesis that phosphorylation and dephosphorylation, possibly of the Na/K/2Cl cotransporter itself, regulates the activity of
...
PMID:The regulation of Na/K/2Cl cotransport and bumetanide binding in avian erythrocytes by protein phosphorylation and dephosphorylation. Effects of kinase inhibitors and okadaic acid. 214 26

C4-leaf phosphoenolpyruvate carboxylase (PEPC; EC 4.1.1.31) undergoes reversible, light-induced increases in its activity-seryl phosphorylation-status in vivo. We now report that the PEPC-protein kinase activity in desalted crude extracts of light-adapted maize leaves is several-fold greater than that from the corresponding dark tissue when in vitro phosphorylation assays are performed with either endogenous or purified dark-form maize PEPC as substrate, both in the absence or presence of okadaic acid, a potent inhibitor of the PEPC type 2A protein phosphatase(s). These and related results indicate that the PEPC protein-serine kinase(s) per se is reversibly light activated in vivo by either covalent modification, protein turnover or, less likely, a tight-binding effector.
...
PMID:Reversible light activation of the phosphoenolpyruvate carboxylase protein-serine kinase in maize leaves. 214 59

The in vivo phosphorylation stoichiometries of 4 serines on the glycogen-binding (G)-subunit of protein phosphatase 1 (PP1) have been determined. In fed rabbits injected with propranolol stoichiometries (mol/mol) were: site 1 (0.67 +/- 0.09), site 2 (0.20 +/- 0.07), site 3a (0.23 +/- 0.01) and site 3b (0). After injection with adrenalin they became: site 1 (0.90 +/- 0.02), site 2 (0.72 +/- 0.01), site 3a (0.23 +/- 0.02) and site 3b (0). These results, together with other data, establish that site 2 phosphorylation by cyclic AMP-dependent protein kinase triggers dissociation of PP1 from the G-subunit in vivo. They also demonstrate that a residue phosphorylated in vitro by glycogen synthase kinase 3 (site 3a) is phosphorylated in vivo.
...
PMID:Identification of three in vivo phosphorylation sites on the glycogen-binding subunit of protein phosphatase 1 from rabbit skeletal muscle, and their response to adrenaline. 215 82

Two forms of type-1 protein phosphatase activating factor (FA) termed FA1 and FA2 have been identified in plasma membranes of pig brain. FA1 is spontaneously active and trypsin-labile whereas FA2 is inactive and trypsin-resistant. Phospholipid reconstitution studies further indicate that the FA activity in the neutral phospholipids-reconstituted complex is spontaneously active and trypsin-labile whereas the FA activity in the acidic phospholipids-reconstituted complex is trypsin-resistant and inactive. The results indicate that inactive FA2 may have its catalytic domain interacted with negatively-charged phospholipids in brain membranes. This provides initial evidence for the regulation of protein kinase FA (a transmembrane signal of insulin and epidermal growth factor) in the central nervous system.
...
PMID:Regulation of protein kinase FA (a transmembrane signal of insulin and epidermal growth factor) in the brain. 215 99

MAP kinase (relative molecular mass, 42,000), a low abundance serine--threonine protein kinase, is transiently activated in many cell types by a variety of mitogens, including insulin, epidermal growth factor, and phorbol esters. In vitro, MAP kinase will phosphorylate and reactivate S6 kinase II previously inactivated by phosphatase treatment. Because many of the stimuli that activate MAP kinase are also stimulators of cell proliferation, and regulation of the cell cycle seems to involve a network of protein kinases, MAP kinase could be important in the transmission of stimuli eventually leading to the progression from G0 to G1 in the cell cycle. Activated MAP kinase contains both phosphotyrosine and phosphothreonine. We report here that MAP kinase can be deactivated completely by treatment with either phosphatase 2A, a protein phosphatase specific for phosphoserine and phosphothreonine, or CD45, a phosphotyrosine-specific protein phosphatase. We demonstrate that MAP kinase is only active when both tyrosyl and threonyl residues are phosphorylated and suggest therefore that the enzyme functions in vivo to integrate signals from two distinct transduction pathways.
...
PMID:Requirement for integration of signals from two distinct phosphorylation pathways for activation of MAP kinase. 215 96

The amount of protein phosphatase 1 (PP1) activity in rabbit skeletal muscle associated with membranes (predominantly sarcoplasmic reticulum) is similar to that bound to glycogen-protein particles. Membrane-vesicle-associated (sarcovesicular) PP1 can be solubilised with 0.5% Triton X-100 (but not 0.5M NaCl) and is complexed to a protein that is structurally and functionally very similar or identical to the G subunit which targets PP1 to glycogen-protein particles. This conclusion is based on immunoblotting and immunotitration experiments using two different preparations of G-subunit-specific antibodies, binding of Triton-solubilised sarcovesicular enzyme to glycogen, stimulation of phosphorylase phosphatase activity by glycogen, phosphorylation of the same tryptic peptides by cyclic-AMP-dependent protein kinase (A-kinase) and release of catalytic subunit following phosphorylation by A-kinase. Membrane-association is not mediated via glycogen because sarcovesicular PP1 is (1) not released by digestion with alpha-amylase or at dilutions which fully dissociate the glycogen-bound enzyme, and (2) is solubilised by Triton X-100 (whereas glycogen-associated PP1 is not). These findings demonstrate that sarcovesicular PP1 is highly homologous to, or the same as, glycogen-associated PP1G and raises the possibility that a common targetting subunit may direct PP1 to different subcellular locations.
...
PMID:Targetting of protein phosphatase 1 to the sarcoplasmic reticulum of rabbit skeletal muscle by a protein that is very similar or identical to the G subunit that directs the enzyme to glycogen. 215 75

Exogenous beta casein, previously phosphorylated in vitro by protein kinase A and casein kinase II, was microinjected into Xenopus oocytes to monitor in vivo protein phosphatase activities. Phosphatase activities were 1.6 and 3.4 fmol/min/oocyte, respectively, for beta casein phosphorylated by casein kinase II and beta casein phosphorylated by protein kinase A. Progesterone induced an early decrease (35% after 10 min) in phosphatase activity restricted to the protein kinase A sites of beta casein.
...
PMID:In vivo progesterone regulation of protein phosphatase activity in Xenopus oocytes. 215 29

Protein kinase FA (an activating factor of ATP.Mg-dependent protein phosphatase) has been characterized to exist in two forms in the purified brain myelin. One form of kinase FA is spontaneously active and trypsin-labile, whereas the other form of kinase FA is inactive and trypsin-resistant, suggesting a different membrane topography with active FA exposed on the outer face of the myelin membrane and inactive FA buried within the myelin membrane. When myelin was solubilized in 1% Triton X-100, all kinase FA became active and trypsin-labile. Phospholipid reconstitution studies further indicated that when kinase FA was reconstituted in acidic phospholipids, such as phosphatidylinositol and phosphatidylserine, the enzyme activity was inhibited in a dose-dependent manner, suggesting that kinase FA interacts with acidic phospholipids which inhibit its activity. Furthermore, when myelin was incubated with exogenous phospholipase C, the inactive/trypsin-resistant FA could be converted to the active/trypsin-labile FA in a time- and dose-dependent manner. Taken together, it is concluded that membrane phospholipids play an important role in modulating the activity of kinase FA in the brain myelin. It is suggested that phospholipase C may mediate the activation-sequestration of inactive/trypsin-resistant kinase FA in the brain myelin through the phospholipase C-catalyzed degradation of acidic membrane phospholipids. The activation-sequestration of protein kinase FA may represent one mode of control modulating the activity of kinase FA in the central nervous system myelin.
...
PMID:On the mechanism of activation of protein kinase FA (an activating factor of ATP.Mg-dependent protein phosphatase) in brain myelin. 216 Feb 45

PC-12 pheochromocytoma cells contain a growth factor-sensitive protein kinase that phosphorylates microtubule associated protein 2 (MAP-2). This MAP kinase is also activated by the protein phosphatase inhibitor okadaic acid (OA). Additionally, OA potentiates the NGF-dependent activation of MAP kinase, but causes only a modest potentiation (20%) of the maximal activation observed with EGF. Since OA is a specific serine/threonine phosphatase inhibitor, these results suggest that serine/threonine phosphorylation may be involved in the hormonal regulation of MAP kinase.
...
PMID:Okadaic acid stimulates the activity of microtubule associated protein kinase in PC-12 pheochromocytoma cells. 216 Dec 19

Three interconvertible forms of the estrogen receptor have been identified in the oviduct of estrogen-stimulated chicks. The non-estradiol binding form (Rnb) can be converted to the lower affinity binding form (Ry, Kd = 0.8 nM) by a process requiring the gamma-phosphoryl moiety of ATP. The enzymatic activity (Fy) essential for this "receptor potentiation" has been isolated from oviduct cytosol using ammonium sulfate fractionation, DEAE chromatography, and HPLC size-exclusion chromatography. The potentiation appears to require both kinase and phosphatase activities. The Fy kinase characteristically phosphorylates casein, histones, and glycogen synthase. Comparison of the kinase with casein kinase II, which also phosphorylates casein and glycogen synthase, indicates that Fy represents a distinct protein kinase since its activity is not stimulated by spermine or inhibited by heparin. Fy-mediated conversion of Rnb to Ry is blocked by the phosphatase inhibitors vanadate, fluoride, and pyrophosphate. The substrate specificity of the Fy phosphatase activity is distinct from that of the two well-characterized protein phosphatases 1 and 2A. Moreover, the requirement for Fy phosphatase activity in converting Rnb to Ry could not be mimicked by its substitution with purified protein phosphatases 1 or 2A. The unique substrate specificity of the oviduct protein phosphatase and protein kinase, which are apparently necessary to confer estradiol binding characteristics to the receptor, implies that these enzymes play a key role in the control of the estrogen receptor in its function as a transcription factor.
...
PMID:Receptor interconversion model of hormone action. 2. Requirement of both kinase and phosphatase activities for conferring estrogen binding activity to the estrogen receptor. 216 Dec 54


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

---