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 magnesium-dependent heparin-inhibited protein kinase activity associated with brain microtubule preparations has been identified as casein kinase II using a monospecific polyclonal antibody. This enzyme appears enriched in cold-stable microtubule fractions. By immunofluorescence microscopy using an antiserum against casein kinase II, the in situ immunolabeling of some microtubule assays has been observed. Thus, mitotic spindles are stained by the anti-casein kinase II antibody in fibroblast cells. In neuroblastoma cells induced to differentiate, the labeling of microtubule arrays inside developing axon-like processes is also seen. These results support the view that casein kinase II can modulate cytoskeletal assembly and dynamics through phosphorylation of microtubule proteins.
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PMID:Association of casein kinase II with microtubules. 264 49

We isolated a novel class of Schizosaccharomyces pombe cold-sensitive mutants with deformed nuclear chromosome domains consisting of thread- or rodlike condensed segments at restrictive temperature. Their mutations were mapped in a novel, identical locus designated crm1 (chromosomal region maintenance). The crm1 mutants also show the following phenotypes. DNA, RNA, and protein syntheses diminish at restrictive temperature. At permissive temperature, the amount of one particular protein, p25, greatly increases. The mutant growth is hypersensitive to Ca2+ and resistant to protein kinase inhibitors. We cloned the 4.1-kb-long crm1+ gene that rescued the above phenotypes by transformation and determined its nucleotide sequence, which predicts a 1,077-residue protein. Affinity-purified antiserum raised against the crm1+ polypeptide expressed in Escherichia coli detected a 115-kD protein in S. pombe extracts. Genomic Southern hybridization and immunoblotting suggested that the crm1+ product might be highly conserved in distant organisms. Through immunofluorescence microscopy, the crm1+ protein appeared to be principally localized within the nucleus and also at its periphery. We speculate that the crm1+ protein might be one of those nuclear components that modify the chromosome structures or regulate the nuclear environment required for maintaining higher order chromosome structures.
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PMID:Higher order chromosome structure is affected by cold-sensitive mutations in a Schizosaccharomyces pombe gene crm1+ which encodes a 115-kD protein preferentially localized in the nucleus and its periphery. 264 65

To explain the insulin resistance induced by catecholamines, we studied the tyrosine kinase activity of insulin receptors in a state characterized by elevated noradrenaline concentrations in vivo, i.e. cold-acclimation. Insulin receptors were partially purified from brown adipose tissue of 3-week- or 48 h-cold-acclimated mice. Insulin-stimulated receptor autophosphorylation and tyrosine kinase activity of insulin receptors prepared from cold-acclimated mice were decreased. Since the effect of noradrenaline is mediated by cyclic AMP and cyclic AMP-dependent protein kinase, we tested the effect of the purified catalytic subunit of this enzyme on insulin receptors purified by wheat-germ agglutinin chromatography. The catalytic subunit had no effect on basal phosphorylation, but completely inhibited the insulin-stimulated receptor phosphorylation. Similarly, receptor kinase activity towards exogenous substrates such as histone or a tyrosine-containing copolymer was abolished. This inhibitory effect was observed with receptors prepared from brown adipose tissue, isolated hepatocytes and skeletal muscle. The same results were obtained on epidermal-growth-factor receptors. Further, the catalytic subunit exerted a comparable effect on the phosphorylation of highly purified insulin receptors. To explain this inhibition, we were able to rule out the following phenomena: a change in insulin binding, a change in the Km of the enzyme for ATP, activation of a phosphatase activity present in the insulin-receptor preparation, depletion of ATP, and phosphorylation of a serine residue of the receptor. These results suggest that the alteration in the insulin-receptor tyrosine kinase activity induced by cyclic AMP-dependent protein kinase could contribute to the insulin resistance produced by catecholamines.
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PMID:Effect of cyclic AMP-dependent protein kinase on insulin receptor tyrosine kinase activity. 282 14

Four mutants with amino acid substitution(s) at or near the putative phosphorylation site (Arg142 Arg143 Thr144 Ser145) of the regulatory subunit of cAMP-dependent protein kinase were obtained by site-directed mutagenesis. Three mutants, BCY1A1a145 (Ser145 to Ala), BCY1His143 (Arg143 to His) and BCY1Asn144, Ala145 (Thr144 to Asn and Ser145 to Ala) complemented a bcy1 mutant, whereas BCY1Gly143 (Arg143 to Gly) did not. In addition, mutant, BCY1Asn144, Ala145 exhibited a dominant cold-sensitive phenotype, which can be most easily explained by the functional alteration of the regulatory subunit of cAMP-dependent protein kinase by the mutations. Analyses of these mutant genes revealed that phosphorylation of the regulatory subunit is not a prerequisite for the regulation of the cAMP-dependent protein kinase activity in responding to the cAMP level.
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PMID:Mutant regulatory subunit of 3',5'-cAMP-dependent protein kinase of yeast Saccharomyces cerevisiae. 282 90

The extent of activation of rat submandibular protein kinase A (EC 2.7.1.37) isozymes following beta-adrenergic receptor stimulation was determined in vitro using dispersed cells and an 8-N3-[32P]cAMP photoprobe. The half-maximal binding of the photoprobe for microsomal and cytosolic type I and cytosolic type II was 9 nM, 27 nM and 92 nM, respectively. 'Cold trap' studies indicated that 70% of type I protein kinase A was activated following maximal beta-adrenergic receptor stimulation, whereas type II activation was less than 40%. Both cytosolic and microsomal type I activation occurred rapidly following beta-adrenergic receptor stimulation and both remain activated throughout the entire secretory period. Type I inactivation occurred rapidly subsequent to beta-adrenergic receptor blockade. The dose-response relationship for the isotypes following beta-adrenergic receptor activation demonstrated a greater extent of type I activation at submaximal concentrations of agonist. Although protein kinase A may not be the only kinase involved in rat submandibular mucin release, these data add further support to a direct regulatory role for this kinase, with type I having potentially a greater role than type II.
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PMID:Subcellular distribution and activation of rat submandibular cAMP-dependent protein kinase following beta-adrenergic receptor stimulation. 283 98

The pituitary of goitrogen-treated White Leghorn cockerels is smaller in size than control birds and the pituitaries of castrated cockerels is nearly twice the size of control birds. The pituitary cells generated by these treatments may not be functional thyrotrophs or gonadotrophs and may not be able to respond to their usual stimuli. Low ambient temperature is a well-known stimulus to the thyroid gland acting through pituitary TSH. Cyclic-AMP-dependent protein kinase activity levels are used here as an index of cellular activity in the pituitary and thyroid glands. Castrated cockerels with or without methimazole treatment do not have an increased pituitary cAMP-dependent protein kinase activity in cold. Methimazole-treated birds have an exaggerated pituitary protein kinase response to cold stress when compared with controls. Pituitary cAMP-dependent protein kinase activity is paralleled by a similar activity increase in the thyroid gland of methimazole-treated cockerels and no increase in the thyroid of castrated birds. Castrated birds at all temperatures have an elevated thyroid cAMP-dependent protein kinase activity ratio which is interpreted as the result of removal of testosterone inhibition.
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PMID:The effects of castration and/or methimazole feeding on the pituitary response to temperature extremes by cockerels. 300 Aug 64

Rat prolactin exhibits microheterogeneity when examined in electrophoretic systems, running as three isoforms having the same molecular weight but different net charges (prolactins 1, 2, and 3 with isoform 3 being the most acidic). As there is precedent for the phosphorylation of a pituitary hormone and phosphorylation is a common cause of microheterogeneity, we examined the possibility that rat prolactin existed in differentially phosphorylated forms. The investigation included examinations of rat prolactin phosphorylation both in vitro and in vivo. For the in vitro studies, purified rat prolactin was incubated with [gamma-32P]ATP and low levels of each of five purified protein kinases. Phosphorylated rat prolactin was identified by autoradiography of silver-stained one- and two-dimensional gels. For the in vivo studies, rat anterior pituitary cells in primary culture were incubated in the presence of H3 32PO4 for 2 or 12 h, after which time the proteins were extracted from the cells, cold acetone-precipitated, or immunoprecipitated and run on two-dimensional gels. We report the in vitro phosphorylation of rat prolactin by cAMP-dependent protein kinase, casein kinase I, protease-activated kinase I, and the calcium/phospholipid-dependent kinase, that phosphorylation with these kinases results in phosphate incorporation only into isoforms 2 and 3, and the phosphorylation of prolactin in rat pituitary cells in primary culture.
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PMID:Phosphorylation of prolactin. 300 80

In the experiments described above, a neutralizing anti-ras antibody was utilized to study the role of ras protein in normal cell proliferation. Initially, it was demonstrated that the antibody was specific for ras protein, and that ras activity was efficiently inhibited. With the neutralizing antibody, it was first shown that ras activity is required for the proliferation of all normal cell types tested. ras activity was required just prior to initiation of S phase. The transforming activity of several retroviral oncogenes was also blocked following anti-ras injection. This included the tyrosine kinase, plasma-membrane-associated proteins, and an oncogene derived from a growth factor. On the other hand, cytoplasmic oncogenes with serine kinase activity were not dependent on ras activity for expression of the transformed phenotype. These observations form the basis of our model for proliferative signal transduction. We propose that the action of either growth factors, their receptor molecules, or related oncogenes initiate an intracellular signal received by ras proteins and then transferred by ras to cytoplasmic serine kinase oncogenes. This signal transduction system directly regulates cellular proliferation. Although further evidence in support of this model is needed, it appears from our studies that the mechanism of signaling between tyrosine kinases and ras proteins might be at the level of phospholipid metabolism. This observation is based on the fact that the mitogenic lipid molecules tested were remarkably dependent on ras activity, even more so than the growth factors or related oncogenes tested. Finally, our work suggests a fundamental distinction between normal and tumor cells. All the normal cell types tested were efficiently inhibited in proliferation by the injected antibody. Tumor cells, on the other hand, were never completely inhibited by the antibody and often were not inhibited at all. The presence of an activated ras oncogene within the tumor assured at least a partial role for ras activity in the proliferation of the mature tumor line. The significance of the observed distinction between normal and tumor cells is not known. The fact that this distinction involves a protein with an apparently critical role in normal proliferation suggests that the observation might be important.
Cold Spring Harb Symp Quant Biol 1988
PMID:Critical role of cellular ras proteins in proliferative signal transduction. 307 1

A cold-sensitive (cs) allele of cdc2, a gene that acts in both the G1 and G2 phases of the fission yeast cell cycle, has been isolated by classical mutagenesis. Further mutagenesis of a cdc2cs strain yielded an extragenic suppressor that rescued the cs cell cycle defect but simultaneously conferred a temperature-sensitive (ts) cdc phenotype. This suppressor mutation was shown to be an allele of cdc13, a previously identified gene. A variety of allele-specific interactions between cdc2 and cdc13 were discovered. These included suppression of cdc13ts alleles by introduction of the cdc2+ gene on a multi-copy plasmid vector. cdc13+ is required in G2 for mitotic initiation and was shown to play no role in the G1 phase of the cell cycle. cdc2+, however, is essential in G1 for DNA replication and in G2 for mitosis. The newly isolated cs allele of cdc2 that is rescued by a ts allele of cdc13 is defective only in its G2 function. cdc13+ cooperates with cdc2+ in the initiation of mitosis but not in the regulation of DNA replication. We propose that the cdc13+ gene product might be a G2-specific substrate of the cdc2+ protein kinase.
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PMID:Interaction between cdc13+ and cdc2+ in the control of mitosis in fission yeast; dissociation of the G1 and G2 roles of the cdc2+ protein kinase. 342 62

Protein phosphorylation at tyrosine residues is believed to be involved in several important cellular processes because tyrosine-specific protein kinase activation is associated with stimulation of cellular proliferation by hormones and growth factors, embryogenesis, and retroviral cell transformation. Because cell proliferation is thought to be an essential component of chemical carcinogenesis, liver tyrosine-specific protein kinase activity was examined during the early stages of the Solt and Farber chemical hepatocarcinogenesis model. Rats were given diethylnitrosamine in one dose (200 mg/kg, IP) followed by 2 weeks of dietary 0.02% 2-acetylamino-fluorene starting at day 14 after diethylnitrosamine, followed by partial hepatectomy on day 21. By day 32 this regimen produces a relatively synchronized population of hyperplastic liver nodules up to 1.5 mm in diameter. Rats were sacrificed on day 32, their livers were perfused with cold normal saline, homogenized, and centrifuged at 1,000g for 10 min. The resulting supernatant was centrifuged at 30,000g for 30 min and the pellet was assayed for tyrosine kinase activity using the synthetic peptide [Val5]angiotensin II as substrate. Rats that received the complete regimen had a 2.6-fold increase in their liver tyrosine kinase activity as compared to sham controls (2.4 pmoles/min/mg protein vs 6.4 pmoles/min/mg protein, P less than .05). In contrast, rats that received a partial regimen (ie, partial hepatectomy, or 2-acetylaminofluorene + partial hepatectomy, or diethylnitrosamine + 2-acetylaminofluorene) did not have elevated tyrosine kinase activity nor did they have hyperplastic nodules. These preliminary data suggest that activation of liver tyrosine kinase is associated with the very early stages of chemical hepatocarcinogenesis.
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PMID:Liver tyrosine kinase activation during early stages of chemical hepatocarcinogenesis. 403 31


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