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

A protein kinase characterized by its ability to phosphorylate microtubule-associated protein-2 (MAP2) and myelin basic protein (MBP) is thought to play a pivotal role in the transduction of signals from many receptors in response to their ligands. A kinase with such activity, named extracellular signal-regulated kinase 1 (ERK1), is activated rapidly by numerous extracellular signals, requires phosphorylation on tyrosine to be fully active, and in vitro can activate a kinase (a ribosomal S6 protein kinase) that is downstream in phosphorylation cascades. From the protein sequence predicted by the rat ERK1 cDNA, peptides were synthesized and used to elicit antibodies. The antibodies recognize both ERK1; a closely related kinase, ERK2; and a third novel ERK-related protein. Using these antibodies we have determined that ERK1 and ERK2 are ubiquitously distributed in rat tissues. Both enzymes are expressed most highly in brain and spinal cord as are their mRNAs. The third ERK protein was found in spinal cord and in testes. The antibodies detect ERKs in cell lines from multiple species, including human, mouse, dog, chicken, and frog, in addition to rat, indicating that the kinases are conserved across species. ERK1 and ERK2 have been separated by chromatography on Mono Q. Stimulation by insulin increases the phosphorylation of both kinases on tyrosine residues, as assessed by immunoblotting with phosphotyrosine antibodies, and retards their elution from Mono Q. Each of these ERKs appears to account for a distinct peak of MBP kinase activity. The activity in each peak is diminished by incubation with either phosphatase 2a or CD45. Therefore, both enzymes have similar modes of regulation and appear to contribute to the growth factor-stimulated MAP2/MBP kinase activity measured in cell extracts.
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PMID:Identification of multiple extracellular signal-regulated kinases (ERKs) with antipeptide antibodies. 165 26

Regulation of prostaglandin (PG) E2 receptors was investigated in a 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate-solubilized fraction from the synaptic membrane of porcine temporal cortex. The fraction was preincubated with exogenous protein kinases, and then the binding of PGE2 was measured. PGE2 binding was increased approximately twofold by pretreatment with the catalytic subunit of cyclic AMP-dependent protein kinase (A kinase) or calmodulin-dependent protein kinase II but not by that with protein kinase C. The increase was dependent on the ATP concentration, with ED50 values being close to the Km values of these protein kinases. Protein kinase inhibitors specific for A kinase and for calmodulin-dependent protein kinase II abolished the effect in a dose-dependent manner, with IC50 values being similar to those reported. Further study using the catalytic subunit of A kinase revealed that the maximal binding capacity apparently increased without affecting the affinity and the rate constants for association and dissociation. On the other hand, acid phosphatase treatment reduced the binding activity to the level of nonspecific binding. In addition, treatment by A kinase did not affect the binding of guanosine 5'-(3-thiotriphosphate) by the GTP-binding proteins and the activation of adenylate cyclase mediated by stimulatory guanine nucleotide-binding regulatory protein, and therefore the phosphorylation is believed to occur on the receptor protein. The results suggest that the PGE2 receptor can take active phosphorylated and inactive dephosphorylated forms, of which only the phosphorylated one can bind PGE2.
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PMID:Regulation of prostaglandin E2 receptor binding activity in porcine temporal cortex by protein phosphorylation. 165 90

The P0 protein in mammalian PNS myelin is known to undergo several posttranslational modifications, such as glycosylation, acylation, sulfation, and phosphorylation. Phosphorylation of purified P0 protein in vitro was studied comparatively using three enzymes, i.e., calcium/phospholipid-dependent protein kinase (protein kinase C), calcium/calmodulin-dependent protein kinase II (CaM kinase II), and the catalytic subunit of cyclic AMP-dependent protein kinase (A kinase). The phosphorylation of P0 protein by CaM kinase II was the greatest, followed by that by protein kinase C; phosphorylation by A kinase, however, was much lower. In order to identify phosphorylation sites, P0 protein was phosphorylated with [32P]ATP and each kinase and then digested with lysylendopeptidase. The resulting phosphopeptides were isolated by HPLC. Subsequent amino acid sequence analysis and comparison with the known sequence of P0 protein revealed that Ser181 and Ser204 were strongly phosphorylated by both protein kinase C and CaM kinase II. In addition, Ser214 was also phosphorylated by protein kinase C, but not by CaM kinase II. Because all of these sites are located in the cytoplasmic domain of P0 protein, phosphorylation may be important for maintenance of the major dense line of PNS myelin.
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PMID:Phosphorylation of P0 glycoprotein in peripheral nerve myelin. 170 69

The effect of phosphorylation of insulin receptor with adenosine 3',5'-cyclic monophosphate-dependent protein kinase (A kinase) on its insulin binding activity was investigated by using insulin receptors prepared from rat liver in vitro. A 95 KDa protein was phosphorylated by stimulation of insulin receptor kinase. This protein was also phosphorylated by A kinase. Analysis of phosphoamino acid showed that tyrosine residue(s) was phosphorylated by activation of insulin receptor kinase, whereas phosphoserine and phosphothreonine were dominantly generated by activation of A kinase. [125I] Iodoinsulin binding activity was decreased by prior phosphorylation of the receptor with A kinase. Scatchard analysis showed that the affinity for insulin was decreased by the phosphorylation with A kinase. Although the maximal activity of insulin receptor kinase was not affected by phosphorylation with A kinase, the insulin concentration which induced half maximal activity (ED50) of the receptor kinase was increased by the phosphorylation with A kinase. These results suggested that counter regulatory hormones whose actions are mediated by the generation of adenosine 3',5'-cyclic monophosphate regulate the insulin binding to the alpha subunit through phosphorylation of the beta subunit of insulin receptor.
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PMID:Adenosine 3',5'-cyclic monophosphate-dependent protein kinase (A kinase) regulation of insulin receptor function: phosphorylation of insulin receptor with A kinase decreases the insulin binding activity. 175 36

Adenylate cyclase and cAMP-dependent protein kinase activities in gametocytogenic (LE5) and nongametocytogenic (T9/96) clones of Plasmodium falciparum were compared to explore the role of cAMP in sexual differentiation of the parasite. Basal adenylate cyclase levels were equivalent in the 2 clones. However, cAMP-dependent histone II-A kinase activity was significantly higher in LE5 than in T9/96 over a range of cAMP concentrations. This difference was due to a decreased Vmax for the enzyme in the nongametocytogenic clone and not to an increased Ka for cAMP. Examination of parasite cAMP-binding proteins, likely to be kinase regulatory subunits, by both photoaffinity labeling with [32P]8-N3-cAMP and affinity chromatography of metabolically [35S]methionine-labeled cytosol of cAMP-agarose revealed a 53-kDa cAMP binding protein in both clones and a 49-kDa cAMP-binding protein in T9/96 that was absent in LE5. Our results suggest that T9/96 has lost the ability to undergo gametocytogenesis due to a substantial decrease in cAMP-dependent protein kinase activity rendering the parasite unable to respond to increased intracellular cAMP levels. Moreover, the reduction in cAMP-dependent protein kinase activity may be due to the presence of an alternative regulatory subunit of the kinase.
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PMID:Comparison of adenylate cyclase and cAMP-dependent protein kinase in gametocytogenic and nongametocytogenic clones of Plasmodium falciparum. 204 Sep 46

Null mutations in the gene YAK1, which encodes a protein with sequence homology to known protein kinases, suppress the cell cycle arrest phenotype of mutants lacking the cyclic AMP-dependent protein kinase (A kinase). That is, loss of the YAK1 protein specifically compensates for loss of the A kinase. Here, we show that the protein encoded by YAK1 has protein kinase activity. Yak1 kinase activity is low during exponential growth but is induced at least 50-fold by arrest of cells prior to the completion of S phase. Induction is not observed by arrest at stages later in the cell cycle. Depending on the arrest regimen, induction can occur either by an increase in Yak1 protein levels or by an increase in Yak1 specific activity. Finally, an increase in Yak1 protein levels causes growth arrest of cells with attenuated A kinase activity. These results suggest that Yak1 acts in a pathway parallel to that of the A kinase to negatively regulate cell proliferation.
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PMID:The Saccharomyces cerevisiae YAK1 gene encodes a protein kinase that is induced by arrest early in the cell cycle. 207 7

In both vertebrates and invertebrates, long-term memory differs from short-term in requiring protein synthesis during training. Studies of the gill and siphon withdrawal reflex in Aplysia indicate that similar requirements can be demonstrated at the level of sensory and motor neurons which may participate in memory storage. A single application of serotonin, a transmitter that mediates sensitization, to individual sensory and motor cells in dissociated cell cultures leads to enhanced transmitter release from the sensory neurons that is independent of new macromolecular synthesis. Five applications of serotonin cause a long-term enhancement, lasting one or more days, which requires translation and transcription. Prolonged application or intracellular injection into the sensory neuron of cyclic AMP, a second messenger for the action of serotonin, also produce long-term increases in synaptic strength, suggesting that some of the gene products important for long-term facilitation are cAMP-inducible. In eukaryotic cells, most cAMP-inducible genes so far studied are activated by the cAMP-dependent protein kinase (A kinase), which phosphorylates transcription factors that bind the cAMP-responsive element TGACGTCA. The cAMP-responsive element (CRE) binds a protein dimer of relative molecular mass 43,000, the CRE-binding protein (CREBP), which has been purified and shown to increase transcription when phosphorylated by the A kinase. Here we show that extracts of the Aplysia central nervous system and extracts of sensory neurons contain a set of proteins, including one with properties similar to mammalian CREBPs, that specifically bind the mammalian CRE sequence. Microinjection of the CRE sequence into the nucleus of a sensory neuron selectively blocks the serotonin-induced long-term increase in synaptic strength, without affecting short-term facilitation. Taken together, these observations suggest that one or more CREB-like transcriptional activators are required for long-term facilitation.
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PMID:Injection of the cAMP-responsive element into the nucleus of Aplysia sensory neurons blocks long-term facilitation. 214 68

Treatment of PC12 cells with nerve growth factor (NGF) resulted in the rapid, but transient, activation of a protein kinase which specifically phosphorylated an endogenous 250-kDa cytoskeletal protein (pp250). We report that the microtubule-associated protein, MAP2, is an alternative substrate for the NGF-activated kinase. NGF treatment maximally activated the kinase within 5 min; however, the activity declined with longer exposure to NGF. The enzyme was localized predominantly in microsomal and soluble fractions and phosphorylated MAP2 on serine and threonine residues. The soluble enzyme was fractionated by DEAE chromatography and gel filtration and had an apparent Mr of 45,000. The enzyme was purified to near homogeneity by chromatofocussing and had a pI of 4.9. Kinetic analysis revealed that NGF treatment caused a sevenfold increase in Vmax for MAP2. The Km with respect to the MAP2 substrate was approximately 50 nM and was not altered by NGF treatment. A novel feature of the NGF-stimulated enzyme was its sharp dependence on Mn2+ concentration. The active enzyme is likely to be phosphorylated, because inclusion of phosphatase inhibitors was required for recovery of optimal activity and the activity was lost on treatment of the enzyme with alkaline phosphatase. Histones, tubulin, casein, bovine serum albumin, and the ribosomal subunit protein S-6 were not phosphorylated by this enzyme. The NGF-stimulated kinase was distinct from A kinase, C kinase, or other NGF-stimulated kinases. The rapid and transient activation of the protein kinase upon NGF treatment suggests that the enzyme may play a role in signal transduction in PC12 cells.
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PMID:Characterization of a nerve growth factor-stimulated protein kinase in PC12 cells which phosphorylates microtubule-associated protein 2 and pp250. 216 72

A kinase activity of purified bovine brain clathrin-coated vesicles phosphorylates the bovine cation-independent mannose 6-phosphate receptor (CI-MPR) with high efficiency (Km approximately 50-100 nM). The kinase copurifies in gel filtration, adsorption on hydroxylapatite, and ion exchange chromatography with the HAI assembly proteins which are part of the coat of Golgi-derived clathrin-coated vesicles. The kinase is associated to the 47-kDa subunit of the complex and exhibits properties similar to a casein kinase II: it uses either ATP or GTP as substrate and its activity is stimulated by poly-L-lysine and inhibited by heparin. Using different domains of the CI-MPR as potential substrates, we show that the phosphorylation is restricted to its cytoplasmic domain. Inhibition studies using synthetic peptides and two-dimensional mapping of the tryptic phosphopeptides indicate that this posttranslational modification occurs on serines 2421 and 2492 of the full-length bovine CI-MPR precursor, residues which are located in typical casein-kinase II recognition sequences. Labeling of Madin-Darby bovine kidney cells followed by immunoprecipitation of the CI-MPR and analysis of the corresponding tryptic phosphopeptides shows that the same serines are phosphorylated in vivo.
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PMID:Phosphorylation of the cytoplasmic domain of the bovine cation-independent mannose 6-phosphate receptor. Serines 2421 and 2492 are the targets of a casein kinase II associated to the Golgi-derived HAI adaptor complex. 217 36

1. The whole-cell variation of the patch clamp technique was used to study the effect of the purified catalytic subunit of the cyclic AMP-dependent protein kinase (A kinase catalytic subunit: AK-C) on the calcium current components of acutely dissociated rat nodose ganglion neurones. 2. The transient low-threshold calcium current component (T) was stable during whole-cell recording. In contrast, currents containing the transient high-threshold (N) and slowly inactivating high-threshold (L) current components declined steadily after stabilization of the currents during the first 5-7 min of recording. When AK-C was included in the recording pipette at physiological concentrations (50 micrograms/ml, approximately 1 microM), currents containing the N- and L-components increased in magnitude beginning 7-9 min after patch rupture, but there was no effect on the isolated T-current. The current-voltage relation of the T-current component was similar to controls, but the current-voltage relation for the N- and L-current components was shifted slightly to more depolarized clamp potentials (Vc), approximately 10 mV. 3. The effect of AK-C on currents containing the N- and L-currents was concentration dependent. There was no effect of 0.1 microgram/ml AK-C, the lowest concentration tested. Currents evoked from holding potentials (Vh) = -80 mV increased 5-10% during a 20 min recording in the presence of 1 microgram/ml AK-C and 30-35% in the presence of 50 micrograms/ml AK-C. In contrast, currents evoked from Vh = -40 mV increased 5-10% in the presence of either 1 or 50 micrograms/ml AK-C. The increase in current magnitude was associated with an increased rate of current inactivation and was evident particularly in currents evoked from Vh = -80 mV. 4. These effects were blocked by prior incubation of AK-C (1 microgram/ml) with a specific peptide inhibitor (protein kinase inhibitor peptide, PKIP; 0.2 mg/ml). 5. We evoked calcium currents using very long (1 s) voltage commands and modelled the traces using a multiexponential function in order to determine the effects of AK-C on the N- and L-current components. The (curve-fitted) N- and L-current components each declined approximately 50% during a 20 min recording in control neurones.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The cyclic AMP-dependent protein kinase catalytic subunit selectively enhances calcium currents in rat nodose neurones. 217 6


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