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

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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)

We studied the accuracy and reproducibility of the keratoscope PKS 1,000 and keratoanalyser PKA 1,000 (Nidek laboratory). When calibrated steel balls are studied without any precaution, the system is unreliable. The photokeratoscope and the keratoanalyser provide good results only if they are used with care. To use the system, we propose the following schedule. Firstly, take a photograph of a steel ball, then set this picture under the video camera and vary the illumination until the accuracy remains unchanged during repeated calibration. With homogenous and constant illumination, the accuracy is about 0.5 diopter.
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PMID:[Accuracy and reproducibility of Nidek's photokeratoanalyser]. 177 15

5,6-Dichloro-1-(beta-D-ribofuranosyl)benzimidazole (DiCl-RB) is a powerful inhibitor of casein kinase-2 (CK-2) [Zandomeni, R. et al. (1986) J. Biol. Chem. 261, 3414-3420]. Here a series of 17 analogues of DiCl-RB has been employed for studying the specificity and the mode of action of this family of CK-2 inhibitors. The two halogen substituents on the benzene ring are shown to play a prominent role in inhibition, the 5,6-dibromo derivative (DiBr-RB) being fivefold more effective than DiCl-RB (Ki = 2 microM, with GTP as substrate), whereas the difluoro derivative (DiF-RB) is nearly as ineffective as unsubstituted 1-(beta-D-ribofuranosyl)benzimidazole. On the other hand, although some modifications of the ribose group significantly decrease the inhibitory efficiency, the sugar moiety is not strictly required, since dichlorobenzimidazole itself (DiCl-Bz) is an inhibitor almost as good as DiCl-RB. Inhibition of CK-2 by DiCl-RB and by its analogues, DiCl-Bz included, is of the competitive type with respect to the nucleotide substrate, the Ki values being lower with GTP than with ATP. The Ki values of the most potent inhibitor, DiBr-RB, with ATP and GTP, are 6 microM and 2 microM, respectively, denoting an affinity for the enzyme higher than that of the physiological substrates, ATP and GTP. DiBr-RB has been assayed for its inhibitory capacity toward several protein kinase other than CK-2. Protein kinase-C, cAMP-dependent protein kinase, the Ser/Thr protein kinase expressed by Pseudorabies virus, and four different tyrosine protein kinases from spleen, proved insensitive to DiBr-RB concentrations capable of almost entirely suppressing the activity of rat liver and maize seedling CK-2. Casein kinase-1 however is nearly as sensitive as CK-2 to DiBr-RB. Inhibition of CK-1 is also of the competitive type with respect to ATP (Ki = 14 microM). Although the inhibitory spectrum of CK-1 by the various analogues is reminiscent of that observed with CK-2, a remarkable difference is revealed by 5'-phosphorylation of ribose which increases the Ki with CK-2 while decreasing that with CK-1.
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PMID:Ribofuranosyl-benzimidazole derivatives as inhibitors of casein kinase-2 and casein kinase-1. 210 15

Recent work has identified a cascade of membrane bound protein kinases in Ehrlich ascites tumor cells. These enzymes, designated PKL, PKS and PKM, are present in both Ehrlich tumor and mouse brain, but the cascade is active only in the tumor tissue. We have now purified a fourth protein kinase, PKF, that is also associated with this cascade. Protein kinase F prosphorylates PKL and is phosphorylated by PKS. The position of this kinase in the cascade is as follows, where the arrows denote phosphorylation: [Formula: see text] The phosphorylation by PKF, like phosphorylation by the other kinases, is at a tyrosine residue and causes the substrate kinase (PKL) to become active. The role of the tyrosine phosphorylation in activating these kinases is described in detail elsewhere. One result of activation of the cascade is the phosphorylation of the beta subunit of the Na+K+-ATPase, which causes inefficient Na+ pumping and is at last in part responsible for the high aerobic glycolysis of Ehrlich ascites tumor cells. By several criteria protein kinase F from Ehrlich cells is homologous to the src gene product (pp60src) from avian sarcoma viruses. Antiserum raised against PKF and sera from rabbits bearing rous sarcoma virus (RSV)-induced tumors quantitatively precipitate the same 60 kd phosphoprotein from cell lysates of three different RSV-transformed cell lines. Both proteins phosphorylate PKL and a 130 kd cytoskeletal protein (vinculin). The tryptic maps of these proteins are closely similar. Both proteins bind specifically to PKL covalently coupled to Sepharose. We used this latter observation to facilitate the purification of pp60 src from RSV-transformed cells.
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PMID:A mouse homolog to the avian sarcoma virus src protein is a member of a protein kinase cascade. 616 90

During purification of tau protein kinase I and II from the bovine brain extract, a new tau protein kinase was detected and purified with phosphocellulose, gel filtration, S-Sepharose and AF-Heparin column chromatography. The molecular mass of the enzyme was determined to be 32 kDa by gel filtration and activity staining on SDS-PAGE. The enzyme is a Ser/Thr protein kinase phosphorylating tau, beta-tubulin, MAP2 and alpha-casein. Employing many synthetic peptides, the recognition site of this enzyme appears to be -SR-. The enzyme requires no second messenger and is inhibited with high concentration of heparin, but not by inhibitors of CKI. These results indicate that this enzyme, tau-tubulin kinase is novel and distinct from TPKI, II and CKI, II.
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PMID:A novel tau-tubulin kinase from bovine brain. 755 43

The PKC1 gene of the budding yeast Saccharomyces cerevisiae encodes a homolog of the alpha, beta, and gamma isoforms of mammalian protein kinase C (PKC) that is essential for cell growth. Loss of PKC1 function results in a cell lysis defect that is due to a deficiency in cell wall construction. In this study, Pkc1p was modified at its COOH terminus with the influenza virus hemagglutinin epitope and was detected by SDS-polyacrylamide gel electrophoresis as a 145- and 150-kDa doublet when overproduced in yeast cells. Pkc1p displayed intrinsic Ser/Thr protein kinase activity in vitro, possessing a substrate specificity similar to that described for mammalian PKC. Specifically, preferred substrates possess an arginine at position -3 and a basic residue at position +2 relative to the target site. A catalytically inactive missense mutant of Pkc1p failed to complement a pkc1 delta mutant, suggesting that protein kinase activity is required for the biological function of Pkc1p. Both wild-type Pkc1p and the inactive form were isolated as phosphoproteins, indicating that Pkc1p is phosphorylated in vivo by another protein kinase. In vitro protein kinase activity of Pkc1p was not dependent on activating cofactors normally required for stimulation of mammalian PKC. However, mutational incapacitation of the pseudosubstrate site of Pkc1p resulted in constitutive activation of the enzyme, both in vivo and in vitro, suggesting that Pkc1p is normally regulated by a mechanism similar to that of its mammalian counterparts. The apparent molecular mass and substrate specificity of Pkc1p, together with its failure to respond to activating cofactors, suggest that this enzyme is distinct from an enzyme purified previously from budding yeast that has enzymatic properties similar to those of mammalian PKC.
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PMID:Saccharomyces cerevisiae PKC1 encodes a protein kinase C (PKC) homolog with a substrate specificity similar to that of mammalian PKC. 820 5

We previously showed that neurofilaments interact with microtubules (MTs) via their high molecular weight subunits (NF-H) after alkaline phosphatase treatment. Here we studied the effects of phosphorylation of NF-H on this interaction. tau protein kinase II, Ser/Thr protein kinase, phosphorylated NF-H in the tail domain, decreased its electrophoretic mobility to a native level, and also restored its property to be less interactive with MTs. Phosphorylation by cAMP-dependent protein kinase caused no shift of electrophoretic mobility or dissociation from MTs. We conclude that the tail domain of NF-H directly interacts with the MT surface, and the interaction is regulated via phosphorylation of the tail domain of NF-H by Ser/Thr protein kinase like tau protein kinase II. To characterize the binding domain of NF-H on MTs, subtilisin digestion of MTs and competition analysis with the MT binding fragment of tau protein were performed. The dissociation constant of NF-H to subtilisin MTs was higher than that to intact MTs. The maximum binding of NF-H was reduced when tau fragments existed. These results revealed that the COOH-terminal region of tubulin is involved in the binding to NF-H, and the NF-H and microtubule-associated protein binding domains are closely apposed on the surface of MTs.
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PMID:Interaction of the tail domain of high molecular weight subunits of neurofilaments with the COOH-terminal region of tubulin and its regulation by tau protein kinase II. 822 79

Recent investigations identified a new signal transduction pathway, termed the sphingomyelin pathway, which may mediate the action of tumor necrosis factor (TNF) alpha and interleukin-1 beta (Mathias, S., Younes, A., Kan, C., Orlow, I., Joseph, C., and Kolesnick, R. N. (1993) Science 259, 519-522). This pathway is initiated by hydrolysis of sphingomyelin to ceramide by a neutral sphingomyelinase and stimulation of a ceramide-activated Ser/Thr protein kinase. Recent investigations demonstrated that kinase activity is proline-directed, recognizing substrates in which the phosphoacceptor site is followed by a proline residue. Until now, the kinase has been defined only as a membrane-bound activity capable of phosphorylating a peptide derived from the sequence surrounding Thr669 of the epidermal growth factor receptor. In the present studies, the kinase was quantitatively extracted from membrane with detergent and separated from protein kinase C by anion-exchange chromatography and isoelectric focusing. Ceramide-activated protein kinase was resolved as an exclusively membrane-bound, 97-kDa protein with a pI of 7.05. Kinase activity toward the epidermal growth factor receptor peptide co-purified with activity toward a generic proline-directed substrate, myelin basic protein. Kinase activity was reconstituted by a denaturation-renaturation procedure and demonstrated activity toward self (autophosphorylation) and exogenous substrate (myelin basic protein). Autophosphorylation occurred exclusively on serine residues. These activities were enhanced to 7-fold of control by ceramide and TNF alpha. These investigations provide additional evidence for a role for ceramide-activated protein kinase in signal transduction for TNF alpha.
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PMID:Renaturation and tumor necrosis factor-alpha stimulation of a 97-kDa ceramide-activated protein kinase. 830 Jun 38

The c-raf-1 protooncogene encodes a Ser/Thr protein kinase. A mitogen-activated protein kinase-kinase (MAPKK) purified from bovine brain is phosphorylated and activated 4-9-fold in vitro by c-Raf-1 from mitogen-treated cells. c-Raf-1 protein kinase activity, measured by the phosphorylation of brain MAPKK substrate, is detectably activated within 1 min after addition of platelet-derived growth factor (PDGF) to 3T3 cells, increasing more rapidly than the endogenous NIH 3T3 cell MAPKK activity. c-Raf-1 activation is also induced by insulin, phorbol ester, thrombin, and endothelin. PDGF-, epidermal groth factor-, and insulin-stimulated 32P-c-Raf-1 yield very similar, complex tryptic 32P-peptide maps, wherein only 2 of 10 32P-peptides appear entirely de novo after growth factor addition. Mitogen-activated protein kinase/extracellular signal-regulated kinase-2 can phosphorylate c-Raf-1 in vitro on 4-6 tryptic 32P-peptides, all of which comigrate with tryptic 32P-peptides derived from c-Raf-1 labeled in situ. Mitogen-activated protein kinase phosphorylation of c-Raf-1 in vitro, however, does not 1) generate 32P-peptides that comigrate with those that appear de novo after PDGF or insulin treatment in situ; 2) does not convert c-Raf-1 polypeptides to a slower mobility on SDS-polyacrylamide gel electrophoresis as is seen after PDGF or insulin; 3) does not alter c-Raf-1 kinase activity toward MAPKK. Thus, based on overlapping site specificity, Erk-2 is a viable candidate to be among the PDGF-stimulated c-Raf-1 kinases. Although PDGF/insulin-stimulated c-Raf-1 Ser/Thr phosphorylation may be necessary to sustain the active state, a role for mitogen-activated protein kinase/extracellular signal-regulated kinase-2 phosphorylation in the initiation of c-Raf-1 activation is unlikely.
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PMID:Mitogen regulation of c-Raf-1 protein kinase activity toward mitogen-activated protein kinase-kinase. 834 Apr 22

When 7721 human hepatocarcinoma cells were treated with 100 nM phorbol-12-myristate-13-acetate (PMA), the activity of N-acetylglucosaminyltransferase V(GnT-V) in the cells varied in accordance with the activity of membranous protein kinase C (PKC), but not with that of cytosolic PKC. Quercetin, a non-specific inhibitor of Ser/Thr protein kinase, and D-sphingosine and staurosporine, two specific inhibitors of PKC, blocked the activation of membranous PKC and GnT-V by PMA. Among the three inhibitors, quercetin was least effective. The inhibitory rates of quercetin and staurosporine toward membranous PKC and GnTV were proportional to the concentrations of the two inhibitors. The activities of GnTV and membranous protein kinase A (PKA) were also induced in parallel by dibutyryl cAMP (db-cAMP) and this induction was blocked by a specific PKA inhibitor. When cell free preparations of 7721 cells and human kidney were treated with alkaline phosphatase (ALP) to remove the phosphate groups, the GnTV activities were decreased. These results suggest that GnTV may be activated by membranous PKC or PKA, indirectly or directly, via phosphorylation of Ser/Thr residues.
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PMID:Regulation of N-acetylglucosaminyltransferase V by protein kinases. 874 53

Eukaryotic polyamine transport systems have not yet been characterized at the molecular level. We have used transposon mutagenesis to identify genes controlling polyamine transport in Saccharomyces cerevisiae. A haploid yeast strain was transformed with a genomic minitransposon- and lacZ-tagged library, and positive clones were selected for growth resistance to methylglyoxal bis(guanylhydrazone) (MGBG), a toxic polyamine analog. A 747-bp DNA fragment adjacent to the lacZ fusion gene rescued from one MGBG-resistant clone mapped to chromosome X within the coding region of a putative Ser/Thr protein kinase gene of previously unknown function (YJR059w, or STK2). A 304-amino-acid stretch comprising 11 of the 12 catalytic subdomains of Stk2p is approximately 83% homologous to the putative Pot1p/Kkt8p (Stk1p) protein kinase, a recently described activator of low-affinity spermine uptake in yeast. Saturable spermidine transport in stk2::lacZ mutants had an approximately fivefold-lower affinity and twofold-lower Vmax than in the parental strain. Transformation of stk2::lacZ cells with the STK2 gene cloned into a single-copy expression vector restored spermidine transport to wild-type levels. Single mutants lacking the catalytic kinase subdomains of STK1 exhibited normal parameters for the initial rate of spermidine transport but showed a time-dependent decrease in total polyamine accumulation and a low-level resistance to toxic polyamine analogs. Spermidine transport was repressed by prior incubation with exogenous spermidine. Exogenous polyamine deprivation also derepressed residual spermidine transport in stk2::lacZ mutants, but simultaneous disruption of STK1 and STK2 virtually abolished high-affinity spermidine transport under both repressed and derepressed conditions. On the other hand, putrescine uptake was also deficient in stk2::lacZ mutants but was not repressed by exogenous spermidine. Interestingly, stk2::lacZ mutants showed increased growth resistance to Li+ and Na+, suggesting a regulatory relationship between polyamine and monovalent inorganic cation transport. These results indicate that the putative STK2 Ser/Thr kinase gene is an essential determinant of high-affinity polyamine transport in yeast whereas its close homolog STK1 mostly affects a lower-affinity, low-capacity polyamine transport activity.
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PMID:The STK2 gene, which encodes a putative Ser/Thr protein kinase, is required for high-affinity spermidine transport in Saccharomyces cerevisiae. 915 97


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