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)

UDP-GlcNAc:Gal beta 3GalNAc-R (GlcNAc to GalNAc) beta 1-6-N-acetylglucosaminyltransferase (i.e. core 2 GlcNAc-T) of the O-linked oligosaccharide pathway is developmentally regulated in human T cells, and changes in its activity have been associated with malignancies and the Wiskott-Aldrich immunodeficiency syndrome. Chinese hamster ovary (CHO) cells normally express low levels of core 2 GlcNAc-T activity (8-12 pmol/mg/h) which can be accurately measured with a two-step assay employing purified bovine beta 1-4Gal-T and high specific activity UDP-[3H]Gal to radiolabel the core 2 reaction product. CHO cells treated with 2 mM sodium butyrate for 24 h exhibited a 16-fold increase in core 2 GlcNAc-T activity, whereas several other differentiating agents including dimethyl sulfoxide, retinoic acid, phorbol ester, and cholera toxin had no effect on activity. The addition of butyrate, cholera toxin, or dimethyl sulfoxide to CHO cells slowed cell proliferation and induced changes in cell morphology characteristic of cell differentiation. Induction of core 2 GlcNAc-T by butyrate was blocked by actinomycin D and cycloheximide. Butyrate treatment also elevated cytosolic cAMP levels with a time course which paralleled, but preceded, induction of core 2 GlcNAc-T activity by approximately 8 h. The protein kinase inhibitors H-7 and H-8 blocked butyrate-dependent induction of enzyme activity, whereas the inactive analogue H1004 had no effect. Core 2 GlcNAc-T showed a change in Km for UDP-GlcNAc, from 0.50 mM in untreated cells to 4.54 mM in butyrate + cholera toxin treated CHO cells, but no changes in Km for the synthetic acceptor, Gal beta 1-3GalNAc alpha-para-nitrophenyl. Despite the 9-fold increase in Km for sugar nucleotide, Vmax/Km was 8.8-fold greater in treated compared with untreated cells. These observations suggest that in CHO cells induction of core 2 GlcNAc-T by butyrate treatment requires de novo gene transcription/translation, activation of protein kinase(s), and is associated with changes in the kinetic properties of the enzyme.
 ...
PMID:Regulation of UDP-GlcNAc:Gal beta 1-3GalNAc-R beta 1-6-N-acetylglucosaminyltransferase (GlcNAc to GalNAc) in Chinese hamster ovary cells. 838 71

The changes in N-acetylglucosaminyltransferase-V and -III (GnT-V, GnT-III) during the cell-cycle of synchronized 7721 human hepatocarcinoma cell line were investigated. Using an HPLC method to assay GnT and flow cytometry (FCM) for cell cycle analysis, it was found that GnT-V showed the highest activity, but GnT-III reached the lowest activity when G(2)/M cells were most abundant. In contrast, GnT-V declined to the minimum while GnT-III elevated to maximum when G(0)/G(1) cells were most predominant. The opposing changes were more obvious when the activities of GnT-V and GnT-III were expressed as relative activities (activity of GnT-V or GnT-III/the sum of activities of GnT-V plus GnT-IV plus GnT-III). These opposing changes of GnT-V and GnT-III during the cell cycle might result from the different regulatory mechanisms of GnT-V and GnT-III expression in the cell cycle. The alterations in the structures of cell surface N-glycans were compatible with the changes of the activities of GnTs. The results from immunocytochemistry and Northern blot showed that the protein and mRNA contents of GnT-V were not significantly changed during the cell cycle. The activity of a cell cycle regulating protein kinase, p34(cdc2) kinase, correlated to the activity of GnT-V. These findings suggested that the change of GnT-V activity in cell cycle was not the consequence of the alteration of gene transcription or enzyme protein synthesis, but might be caused by the post-translational regulation. The decrease in GnT-V and the corresponding increase in GnT-III activities were also found after the cells were treated with all-trans retinoic acid (ATRA), and the mechanism of this might be different from that in the cell cycle.
 ...
PMID:Opposing changes in N-acetylglucosaminyltransferase-V and -III during the cell cycle and all-trans retinoic acid treatment of hepatocarcinoma cell line. 1069 67

O-linked N-acetylglucosaminyltransferase (OGT) catalyzes the transfer of O-linked GlcNAc to serine or threonine residues of a variety of substrate proteins, including nuclear pore proteins, transcription factors, and proteins implicated in diabetes and neurodegenerative disorders. We have identified two nucleocytoplasmic isoforms of OGT (ncOGT and sOGT) and one isoform that localizes to the mitochondria (mOGT). These three isoforms contain identical catalytic regions but differ in the number of tetratricopeptide repeat motifs found at the N-terminus of each enzyme. We expressed each of these OGT isoforms in a soluble form in Escherichia coli and have used them to identify novel targets including the Src-family tyrosine kinase yes and O-GlcNAc-ase. We demonstrate that some substrate proteins, such as Nup62 and casein kinase II, are glycosylated by both ncOGT and mOGT, while others such as O-GlcNAcase and tau are specifically modified by ncOGT. The yes kinase was specifically modified by mOGT. The short isoform of OGT (sOGT) did not glycosylate any of the substrates tested, although it retains a potentially active catalytic domain. Our findings demonstrate the potential utility of recombinant OGT in identifying new targets and illustrate the necessity to examine all active isoforms of the enzyme. The identification of a tyrosine kinase and O-GlcNAcase as OGT targets suggests the potential for OGT participation in numerous signal transduction cascades.
 ...
PMID:Recombinant O-GlcNAc transferase isoforms: identification of O-GlcNAcase, yes tyrosine kinase, and tau as isoform-specific substrates. 1643 89

The glycosylphosphatidylinositol (GPI) anchors are linked to glycosylphosphatidylinositol-anchored proteins (GAPs) which are essential for the growth of mammalian, yeast and protozoan cells. The GPI anchor is covalently linked to GAP by amide bond formation between the carboxyl terminus and phosphoethanolamine attached at the third mannose and mediated by a transamidase complex. Mediation of GPI synthesis is by the sequential additions of GPI-N-acetylglucosaminyltransferase (GPI-GnT) complex, the GlcN-PI de-N-acetylase, the GlcN-PI mannosyltransferases and the GPI lipid anchor phosphoethanolamine transferase complexes. We report a rice gene OsPIG-F that encodes a homolog to the human PIG-F protein, one of GPI lipid anchor phosphoethanolamine transferase complexes. The amino acid sequences of rice PIG-F consisted of six helix transmembrane domains, one glycosaminoglycan attachment site, one cGMP-dependent protein kinase phosphorylation site and a protein C phosphorylation site at the C-terminus. This unique structure of rice PIG-F indicates the typical membrane bound structure of a protein. Polyclonal antibody for rice PIG-F was found to be cross-reactive with a protein extracted from the leaves of rice. The levels of rice PIG-F transcripts were found to be abundant in leaves, moderately in the milky stage of seed development and less in the floral spikelet, indicating that the rice PIG-F gene was differentially regulated in specific tissues. Furthermore, the levels of rice PIG-F transcription were up-regulated by growth hormones including GA(3), NAA and kinetin. These results indicated that the rice PIG-F gene expression may medicated by these growth regulators.
 ...
PMID:Characterization of phosphatidylinositol-glycan biosynthesis protein class F gene in rice. 1785 46