Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.1 (protein kinase)
 81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Casein kinase from lactating bovine mammary gland catalyses the transfer of the terminal phosphoryl group of ATP to specific serine residues in dephosphorylated caseins. Best substrates for casein kinase are the dephosphorylated proteins (bovine alpha S1- and beta-caseins and pepsin), unphosphorylated human beta-casein and the dephosphorylated peptide (residues 1-25) from bovine beta-casein. Results obtained with bovine and human beta-caseins indicate that the two serines underlined in the cluster Ser-Leu-Ser-Ser-Ser are particularly susceptible to the action of casein kinase. Since a similar sequence is found in dephosphorylated alpha S1-casein, it is probable that serines in this region of alpha S1-casein are also phosphorylated. The results support the concept that certain serines in casein are particularly susceptible to phosphorylation by casein kinase.
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PMID:Role of mammary casein kinase in the phosphorylation of milk proteins. 46 41

Both genetic and nongenetic factors predispose to ulcer diathesis. At the mucosal level ulcers result from an imbalance between aggressive factors and mucosal defense. Ulcer therapy reduces aggressive forces, bolsters defense, or both. Gastric acid, the major aggressive factor, may have its secretion inhibited or it may be partially neutralized by antacids. H2 receptor antagonists competitively block histamine occupancy of H2 receptors on parietal cells, thereby preventing stimulation of adenylate cyclase, cAMP rises, and activation of protein kinase and H+/K+ATPase. Prostaglandins inhibit acid secretion largely by preventing histamine-induced cAMP rises. Proton pump inhibitors bind H+/K+ATPase. Antimuscarinics inhibit acetylcholine receptors on the parietal cell, thereby blocking Ca2+ entry and subsequent activation of protein kinase and the proton pump. Mucosal defense is enhanced by certain prostaglandins, colloidal bismuth subcitrate and sucralfate. Prostaglandins stimulate secretion of bicarbonate and mucus, among other effects. Colloidal bismuth and sucralfate bind to proteins in the ulcer base and stimulate bicarbonate and mucus secretion, partially, in the case of sucralfate, by increasing endogenous prostanoid synthesis. Sucralfate also binds pepsin and bile acids. Colloidal bismuth temporarily eradicates mucosal colonization by Campylobacter pylori, another putative agent in ulcer diathesis.
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PMID:The pathophysiological and pharmacological basis of peptic ulcer therapy. 290 42

L-type pyruvate kinase (EC 2.7.1.40) purified from pig liver was ADP-ribosylated by incubation with NAD and ADP-ribosyltransferase purified from hen liver nuclei. Maximal incorporation of the ADP-ribose moiety from NAD into the L-type pyruvate kinase was 0.98 mol/mol of subunit. The Km values for NAD and L-type pyruvate kinase were 0.17 mM and 9.7 microM, respectively. ADP-ribosylation of the L-type pyruvate kinase resulted in suppression of the subsequent phosphorylation catalyzed by cAMP-dependent protein kinase. The ADP-ribosylation-induced suppression of phosphorylation of the L-type pyruvate kinase also resulted in suppression of the phosphorylation-induced inactivation. Amino acid analysis, after exhaustive sequential digestion of ADP-ribosyl-L-type pyruvate kinase with pepsin, aminopeptidase M and carboxy-peptidase B showed arginine to be the ADP-ribose-accepting amino acid. These results together with finding of the ADP-ribosyltransferase activity in mammalian liver cytosol (Moss, J. and Stanley, S.J. (1981) J. Biol. Chem. 256, 7830-7833) suggest that ADP-ribosylation may participate in the regulation of the L-type pyruvate kinase activity through changes in the rate of phosphorylation.
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PMID:ADP-ribosylation suppresses phosphorylation of the L-type pyruvate kinase. 334 9

Both the triple-helical and denatured forms of nonfibrillar bovine dermal type I collagen were tested as substrates for the catalytic subunit of cAMP-dependent protein kinase in an in vitro reaction. Native, triple-helical collagen was not phosphorylated, but collagen that had been thermally denatured into individual alpha chains was a substrate for the protein kinase. Catalytic subunit of cAMP-dependent protein kinase phosphorylated denatured collagen to between 3 to 4 mol of phosphate/mol of (alpha 1(I)2 alpha 2(I). Pepsin-solubilized and intact collagens were phosphorylated similarly, as long as each was in a nonhelical conformation. The first 2 mol of phosphate incorporated into type I collagen by the protein kinase were present in the alpha 2(I) chain. The alpha 1(I) chain was only phosphorylated during long incubations in which the stoichiometry exceeded 2 mol of phosphate/mol of (alpha 1(I)2 alpha 2(I). Phosphoserine was the only phosphoamino acid identified in collagen that had been phosphorylated to any degree by the protein kinase. The 2 mol of phosphate incorporated into the alpha 2(I) chain were localized to the alpha 2(I)CB4 cyanogen bromide fragment. The catalytic subunit of cAMP-dependent protein kinase phosphorylated denatured pepsin-solubilized collagen with a Km of 8 microM and a Vmax of approximately 0.1 mumol/min/mg of enzyme. Denatured, but not triple-helical, type I collagen was also phosphorylated by cGMP-dependent protein kinase, although it was a poorer substrate for this enzyme than for the cAMP-dependent protein kinase. Collagen was not a substrate for phospholipid-sensitive Ca2+-dependent protein kinase. These results suggest the potential for nascent alpha chains of type I collagen to be susceptible to phosphorylation by cAMP-dependent protein kinase in vivo prior to triple-helix formation. Such a phosphorylation of collagen could be relevant to the action of cAMP to increase the intracellular degradation of newly synthesized collagen.
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PMID:In vitro phosphorylation of type I collagen by cyclic AMP-dependent protein kinase. 395 36

The partial purification and characterization of (a) factor(s) from rat brain which inhibit(s) the activity of calcium and phospholipid-dependent protein kinase from the same tissue is described. This factor, present in 100 000 X g rat brain homogenate supernatant, is inactivated upon treatment by trypsin and pepsin and is therefore assumed to be a protein. It was partially purified by ion-exchange chromatography on DEAE-cellulose, ammonium sulfate precipitation and gel filtration. This inhibitor is not stable to heating at 70 degrees C for 10 min, however partial renaturation of the inhibitory activity can be observed after incubation of the denatured inhibitor for 24 h at 4 degrees C. It is precipitable by 10% trichloroacetic acid and by 2 M ammonium sulfate. It exhibits a Stokes radius of 20 A by gel exclusion chromatography, corresponding to a molecular mass of 20 kDa assuming a globular shape. Kinetic analysis of the inhibition of calcium-phospholipid-dependent histone kinase activity indicates that the inhibitor is competitive with respect to the protein substrate. No change was observed in the kinetic values of the kinase for ATP, Ca2+ and phospholipids.
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PMID:A protein kinase C inhibitory activity is present in rat brain homogenate. 623 42

The 350-residue amino acid sequence of the catalytic subunit of bovine cardiac muscle adenosine cyclic 3',5'-phosphate dependent protein kinase is described. The protein has a molecular weight of 40 862, which includes an N-tetradecanoyl (myristyl) group blocking the NH2 terminus and phosphate groups at threonine-197 and serine-338. Seven methionyl bonds in the S-carboxymethylated protein were cleaved with cyanogen bromide to yield eight primary peptides. These fragments, and subpeptides generated by cleavage with trypsin, pepsin, chymotrypsin, thermolysin, and Myxobacter AL-1 protease II, were purified and analyzed to yield the majority of the sequence. The primary peptides were aligned by analyses of overlapping peptides, particularly of methione-containing tryptic peptides generated after in vitro [14C]methyl exchange labeling of methionyl residues in the intact protein.
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PMID:Amino acid sequence of the catalytic subunit of bovine type II adenosine cyclic 3',5'-phosphate dependent protein kinase. 631 Dec 52

Two new sites phosphorylated by rat liver cyclic AMP-independent casein kinase TS have been identified in denatured pepsin and soybean antiprotease C-II, exhibiting the sequences: Cys-Ser-Ser(P)-Ile-Asp-Ser and His-Ser3(P)-Asp-Asp-Glu, respectively. Their phosphorylation efficiency has been compared to that of previously identified sites and the effects of chemical modifications in the vicinity of the phosphorylatable residue have been studied. The results obtained support the following conclusions: 1. All sites affected by casein kinase TS conform to the sequence: Ser/Thr-X-Glu/Asp which is also believed to be required by the mammary gland casein kinase. Threonine appears to be less suitable for phosphorylation then serine. The presence of some additional residues on the C-terminal side also appears to be required. 2. X can be either an additional acidic residue or a natural one, but not a basic residue. The contiguity of an acidic cluster to the C-terminal side of the target greatly improves the phosphorylation efficiency. 3. The residues N-terminal to the target one do not seem to be relevant for determining the site recognition by the protein kinase. 4. The predicted secondary structure constantly occurring at the phosphorylation sites is the beta-turn: apparently the bend must include both the target residue and the acidic determinant at the n + 2 position.
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PMID:A study with model substrates of the structure of the sites phosphorylated by rat liver casein kinase TS. 679 23

Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) was used to determine amide proton/deuteron (H/D) exchange rates. The method has broad application to the study of protein conformation and folding and to the study of protein-ligand interactions and requires no modifications of the instrument. Amide protons were allowed to exchange with deuterons in buffered D2O at room temperature, pD 7.25. Exchanged deuterons were "frozen" in the exchanged state by quenching at pH 2.5, 0 degree C and analyzed by MALDI-TOF MS. The matrix mixture consisted of 5 mg/mL alpha-cyano-4-hydroxycinnamic acid, acetonitrile, ethanol, and 0.1% TFA. The matrix was adjusted to pH 2.5, and the chilled MALDI target was rapidly dried. Deuteration of amide protons on cyclic AMP-dependent protein kinase was measured after short times of incubation in deuterium by pepsin protein digestion and MALDI-TOF MS analysis. The unseparated peptic digest was analyzed in a single spectrum of the mixture. From five spectra, H/D exchange rates were determined for some 40 peptides covering 65% of the protein sequence.
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PMID:Measurement of amide hydrogen exchange by MALDI-TOF mass spectrometry. 978 43

Various proteins/enzymes obtained commercially were tested for the presence of endogenously nitrated tyrosine by Western blot analysis omitting reducing agent in the step of SDS-PAGE. Histones II-S and VIII-S, IgG, cAMP-dependent protein kinase (PKA), phosphorylase b, and phosphorylase kinase exhibited strong immunoreactive bands. Histone VI-S, glycogen synthase, lactate dehydrogenase, actin, thyroglobulin, and macroglobulin exhibited moderate immunoreactivity. Histone III-S, casein, acetyl cholinesterase, DNase I, and lipase had only traceable immunoreactivity. Whereas histone VII-S, pyruvate kinase, trypsin, pepsin, chymotrypsin, protease IV, and protease XIII, and glutathione S-transferase lacked immunoreactivity. A variation of immunoreactivity between hypertensive and normaltensive rat hearts was found in the histone-agarose fractions of crude extracts. Additionally, nitrotyrosine immunoreactivity was observed in non-mammalian organisms including Eschericia coli, Saccharomyces cerevisiae and Triticum vulgaris. Upon the treatment of 15 microM peroxynitrite (PN), strong oxidant derived from nitric oxide (NO), the apparent Km of PKA for cAMP increased from approximately 10(-8) to 10(-6) M. The results imply that the varied nitration of tyrosine residues in proteins/enzymes may occur as a post-translational modification in vivo, and such discriminative nitration may be vital in PN/NO-regulated signal transduction cascade.
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PMID:Protein nitration. 1119 83

cAMP-dependent protein kinase (cAPK) is a key component in numerous cell signaling pathways. The cAPK regulatory (R) subunit maintains the kinase in an inactive state until cAMP saturation of the R-subunit leads to activation of the enzyme. To delineate the conformational changes associated with cAPK activation, the amide hydrogen/deuterium exchange in the cAPK type IIbeta R-subunit was probed by electrospray mass spectrometry. Three states of the R-subunit, cAMP-bound, catalytic (C)-subunit bound, and apo, were incubated in deuterated water for various lengths of time and then, prior to mass spectrometry analysis, subjected to digestion by pepsin to localize the deuterium incorporation. High sequence coverage (>99%) by the pepsin-digested fragments enables us to monitor the dynamics of the whole protein. The effects of cAMP binding on RIIbeta amide hydrogen exchange are restricted to the cAMP-binding pockets, while the effects of C-subunit binding are evident across both cAMP-binding domains and the linker region. The decreased amide hydrogen exchange for residues 253-268 within cAMP binding domain A and for residues 102-115, which include the pseudosubstrate inhibitory site, support the prediction that these two regions represent the conserved primary and peripheral C-subunit binding sites. An increase in amide hydrogen exchange for a broad area within cAMP-binding domain B and a narrow area within cAMP-binding domain A (residues 222-232) suggest that C-subunit binding transmits long-distance conformational changes throughout the protein.
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PMID:Dynamics of cAPK type IIbeta activation revealed by enhanced amide H/2H exchange mass spectrometry (DXMS). 1266 31


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