Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.26 (GSK)
 6,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The roles of casein kinases I and II in the activation of protein phosphatase-1i (PP-1i) by glycogen synthase kinase-3 (GSK-3) were studied using enzyme preparations from porcine heart. PP-1i was activated by GSK-3 and the levels of activation achieved decreased by increasing the ionic strength (0-0.2 M KCl) in the incubation mixtures. At low ionic strength (no KCl added) casein kinase II increased the rate of activation of PP-1i by GSK-3 and the activation proceeded to a slightly greater extent (110-120%) than that obtained by GSK-3 alone. In the presence of 0.14 M KCl only a partial activation of PP-1i by GSK-3 was observed, but when casein kinase II was also added activation was restored to levels observed when PP-1i was activated by GSK-3 in the absence of salt. This effect was shown to be dependent on the concentration of casein kinase II. These results would imply that at low ionic strength casein kinase II and GSK-3 synergistically activate PP-1i as has been previously reported for the rabbit skeletal muscle enzyme (DePaoli-Roach, A. A., J. Biol. Chem. 259, 12144-12152, 1984), whereas, at physiological ionic strength, casein kinase II action may be obligatory for GSK-3 activity. Similar results were obtained when casein kinase I replaced casein kinase II.
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PMID:Hierarchical regulation by casein kinases I and II of the activation of protein phosphatase-1i by glycogen synthase kinase-3 is ionic strength dependent. 838 7

During neurogenesis in Drosophila, groups of equipotential, neurally competent cells choose between epidermal and neural fates. Notch, a phylogenetically conserved transmembrane protein, may act as a receptor in a lateral signalling pathway in which a single neural precursor is chosen from each group and the neural fate of the other cells is inhibited, causing them to differentiate into epidermis. Possible intracellular transduction events mediating signals from Notch are, however, unknown. shaggy is also required for the lateral signal and encodes serine/threonine protein kinases with homology to the glycogen synthase kinase-3 (GSK-3) enzymes that act in signal transduction pathways in vertebrates. We report here that, in transgenic flies, GSK-3 beta can substitute for shaggy, and we also present a study of epistatic relationships between shaggy and gain and loss of function alleles of Notch. The results indicate that shaggy/GSK-3 is part of a signalling pathway downstream of Notch.
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PMID:Drosophila shaggy kinase and rat glycogen synthase kinase-3 have conserved activities and act downstream of Notch. 838 71

Mg-ATP-dependent protein phosphatase activating factor [kinase FA/glycogen synthase kinase 3 (GSK-3)] has been identified in highly purified clathrin-coated vesicles (CCVs) isolated from pig brain. Kinase FA was found to exist in an inactive state but can be activated by 1% Triton X-100 or 1 M Tris-HCl extraction in brain CCVs. Activation of kinase FA in CCVs is due to disassociation of the kinase from CCVs as demonstrated on sucrose density-gradient ultracentrifugation and Sepharose CL-4B gel filtration. Using purified brain CCVs as substrates, kinase FA enhanced the endogenous phosphorylation of assembly protein complexes in the molecular weight range of 100,000-130,000 severalfold, as demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography. Comparisons with well-defined brain CCV-associated endogenous protein kinases such as pp50 kinase/AP50 and casein kinase 2 provide evidence that kinase FA/GSK-3 represents a third potent and unique CCV-associated protein kinase distinctly different from the previously described CCV protein kinases, suggesting the possible involvement of kinase FA in the regulation of CCV functions in the brain. The results also support the notion that protein kinase FA is involved in cell surface signal transduction in the CNS.
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PMID:Identification and characterization of protein kinase FA/glycogen synthase kinase 3 in clathrin-coated brain vesicles. 838 21

Three genes TPK1, TPK2 and TPK3 encode in Saccharomyces cerevisiae distinct catalytic subunits of cAMP-dependent protein kinase (cAPK). We have measured cAPK activity in vitro and, indirectly, in vivo in yeast strains carrying only one of the three TPK genes. The strain containing TPK3 as the only intact TPK gene showed nearly undetectable phosphorylating activity and no TPK3 mRNA could be detected, although the cells grow normally. Overexpression of TPK3 in a high copy vector or under the control of the inducible GAL1 promoter did not by itself result in a corresponding increase in activity but coexpression of BCY1, the gene coding for the regulatory subunit, was necessary in both cases to achieve high levels of phosphorylating activity. Moreover, BCY1 overexpression not only increased Tpk3 catalytic activity but also increased the amount of TPK3 mRNA detected in Northern blots.
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PMID:Low activity of the yeast cAMP-dependent protein kinase catalytic subunit Tpk3 is due to the poor expression of the TPK3 gene. 838 30

The ATP.Mg-dependent protein phosphatase activating factor (FA) has been identified as a microtubule protein kinase and as a microtubule protein phosphatase activator. FA could phosphorylate microtubule-associated tau protein up to 4 moles of phosphates per mole of protein. However, more than 80% of the phosphates in 32P-tau phosphorylated by FA could be removed by ATP.Mg-dependent protein phosphatase and the tau phosphatase activity was FA-dependent. Functional study further revealed that as a tau kinase, FA could phosphorylate tau and thereby inhibits cross-linking copolymerization of tau with tubulin and actin filaments whereas as a tau phosphatase activating factor, FA could promote copolymerization of tau with tubulin and actin filaments. Taken together, the results provide evidence that a cyclic modulation of cytoskeleton assembly-disassembly can be controlled by FA, representing an efficient cyclic cascade mechanism for rapid structural and functional regulation of cytoskeletal system in the central nervous system.
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PMID:Cyclic modulation of cytoskeleton assembly-disassembly by the ATP.Mg-dependent protein phosphatase activator (kinase FA). 839 3

This paper reports on the isolation of a novel class of plant serine/threonine protein kinase genes, MsK-1, MsK-2 and MsK-3. They belong to the superfamily of cdc2-like genes, but show highest identity to the Drosophila shaggy and rat GSK-3 proteins (65-70%). All of these kinases share a highly conserved catalytic protein kinase domain. Different amino-terminal extensions distinguish the different proteins. The different plant kinases do not originate from differential processing of the same gene as is found for shaggy, but are encoded by different members of a gene family. Similarly to the shaggy kinases, the plant kinases show different organ-specific and stage-specific developmental expression patterns. Since the shaggy kinases play an important role in intercellular communication in Drosophila development, the MsK kinases are expected to perform a similar function in plants.
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PMID:The MsK family of alfalfa protein kinase genes encodes homologues of shaggy/glycogen synthase kinase-3 and shows differential expression patterns in plant organs and development. 840 15

The transforming gene of Abelson murine leukaemia virus (v-abl) codes for a membrane-associated tyrosine-specific protein kinase (abl TPK). Analysis of the v-abl gene has shown that both the fibroblast-transforming and tyrosine-protein kinase activities reside within a minimal region encoding a protein of 43 kDa (p43v-abl), which represents the most active, isolated form of this enzyme. Since the cellular substrates for p43v-abl are yet to be identified, we synthesized by classical solution methods the octapeptide H-Gly-Asp-Thr-Tyr-Thr-Ala-His-Ala-OH, corresponding to the structural sequence of the main putative autophosphorylation site (Tyr 515) of the abl TPK, as well as some of its analogs modified in positions -2, -1, +1 and +3. The synthetic peptides were tested as substrates for the p43v-abl. The kinetic data obtained indicate that the rates of their phosphorylation vary considerably depending on the sequence of the peptide, as expected. As a rule, no significant increment of the efficiency results from each substitution in the parent sequence. While the replacement of the two charged residues, namely Asp-2 and His-7, with neutral Ala is well tolerated, the substitution with amino acids bearing opposite charges is detrimental. The correlation between secondary structure of our synthetic octapeptides and their substrate recognition by p43v-abl was studied using CD and fluorescence spectroscopy in 5 mM Tris, in 98% TFE/Tris and in 30 mM SDS solutions. The comparison of the spectroscopic data with the kinetic parameters does not confirm a close relationship between the conformational properties of these peptides and their enzymatic role.
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PMID:Synthesis and conformational studies on peptides corresponding to a putative autophosphorylation site of abl TPK. 846 52

A systematic analysis reveals that out of 20 protein kinases examined, specific for either Ser/Thr or Tyr, the majority are extremely sensitive to staurosporine, with IC50 values in the low nanomolar range. A few of them however, notably protein kinases CK1 and CK2, mitogen-activated protein (MAP) kinase and protein-tyrosine kinase CSK, are relatively refractory to staurosporine inhibition, exhibiting IC50 values in the micromolar range. With all protein kinases tested, namely PKA, CK1, CK2, MAP kinase (ERK-1), c-Fgr, Lyn, CSK and TPK-IIB/p38Syk, staurosporine inhibition was competitive with respect to ATP, regardless of its inhibitory power. In contrast, either uncompetitive or noncompetitive kinetics of inhibition with respect to the phosphoacceptor substrate were exhibited by Ser/Thr and Tyr-specific protein kinases, respectively, consistent with a different mechanism of catalysis by these two sub-families of kinases. Computer modeling based on PKA crystal structure in conjunction with sequence analysis suggest that the low sensitivity to staurosporine of CK2 may be accounted for by the bulky nature of three residues, Val66, Phe113 and Ile174 which are homologous to PKA Ala70, Met120 and Thr183, respectively. In contrast these PKA residues are either conserved or replaced by smaller ones in protein kinases highly sensitive to staurosporine inhibition. On the other hand, His160 which is homologous to PKA Glu170, appears to be responsible for the unique behaviour of CK2 with respect to a staurosporine derivative (CGP44171A) bearing a negatively charged benzoyl substituent: while CGP44171A is 10- 100-fold less effective than staurosporine against PKA and most of the other protein kinases tested, it is actually more effective than staurosporine for CK2 inhibition, but it looses part of its efficacy if it is tested on a CK2 mutant (H160D) in which His160 has been replaced by Asp. It can be concluded from these data that the catalytic sites of protein kinases are divergent enough as to allow a competitive inhibitor like staurosporine to be fairly selective, a feature that can be enhanced by suitable modifications designed based on the structure of the catalytic site of the kinase.
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PMID:Different susceptibility of protein kinases to staurosporine inhibition. Kinetic studies and molecular bases for the resistance of protein kinase CK2. 852 58

We examined the subcellular distribution of two glycogen synthase kinase-3 (GSK-3) isoforms in rat cerebellum. Results from immunoelectron microscopy and subcellular fractionation revealed that one isoform, tau protein kinase I/GSK-3 beta (TPKI/GSK-3 beta), was present in mitochondria, but GSK-3 alpha was not. Although the two GSK-3 isoforms seem to have similar properties, the difference of subcellular localization observed here suggests that TPKI/GSK-3 beta fulfills some specific function in mitochondria.
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PMID:Different localization of tau protein kinase I/glycogen synthase kinase-3 beta from glycogen synthase kinase-3 alpha in cerebellum mitochondria. 857 78

The effects of a series of synthetic oligopeptides on progesterone production by rat CL cells were compared and their mechanism of actions was studied in vitro. The ones with inhibitory actions were characterized by carrying positive charge in the medium of pH 7.3-7.5 and with intermolecular linkage. A preliminary survey of the effect of the active oligopeptides on signal systems showed: (1)GY and YG inhibited PLC system; (2)GY and GSK reduced hCG-induced progesterone production in CL cells probably by regulating cellular Ca2+ concentration; (3) GSK decreased TPK activity and GYK increased it in hCG treated CL cell though both of them were inhibitory on progesterone production. GSK also stimulated PKC and supressed PKA activity in CL cells. The anti-progesterone effect of oligopeptides so far synthesized may influence either PKA or PKC or TPK systems. The mechanism of action at the molecular level is quite complicated.
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PMID:[The effects of synthetic oligopeptides on progesterone production in corpus luteum cell of rat and their mechanism of action]. 858 91


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