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911.
Ingvild Aukrust Lise Bj?rkhaug Maria Negahdar Janne Molnes Bente B. Johansson Yvonne Müller Wilhelm Haas Steven P. Gygi Oddmund S?vik Torgeir Flatmark Rohit N. Kulkarni P?l R. Nj?lstad 《The Journal of biological chemistry》2013,288(8):5951-5962
Glucokinase is the predominant hexokinase expressed in hepatocytes and pancreatic β-cells, with a pivotal role in regulating glucose-stimulated insulin secretion, illustrated by glucokinase gene mutations causing monogenic diabetes and congenital hyperinsulinemic hypoglycemia. A complex tissue-specific network of mechanisms regulates this enzyme, and a major unanswered question in glucokinase biology is how post-translational modifications control the function of the enzyme. Here, we show that the pancreatic isoform of human glucokinase is SUMOylated in vitro, using recombinant enzymes, and in insulin-secreting model cells. Three N-terminal lysines unique for the pancreatic isoform (Lys-12/Lys-13 and/or Lys-15) may represent one SUMOylation site, with an additional site (Lys-346) common for the pancreatic and the liver isoform. SUMO-1 and E2 overexpression stabilized preferentially the wild-type human pancreatic enzyme in MIN6 β-cells, and SUMOylation increased the catalytic activity of recombinant human glucokinase in vitro and also of glucokinase in target cells. Small ubiquitin-like modifier conjugation represents a novel form of post-translational modification of the enzyme, and it may have an important regulatory function in pancreatic β-cells. 相似文献
912.
Sharon LR Simon Lise Lamoureux Margot Plews Michael Stobart Jillian LeMaistre Ute Ziegler Catherine Graham Stefanie Czub Martin Groschup J David Knox 《Proteome science》2008,6(1):23
Background
The bovine spongiform encephalopathy (BSE) epidemic and the emergence of a new human variant of Creutzfeldt-Jakob Disease (vCJD) have led to profound changes in the production and trade of agricultural goods. The rapid tests currently approved for BSE monitoring in slaughtered cattle are all based on the detection of the disease related isoform of the prion protein, PrPd, in brain tissue and consequently are only suitable for post-mortem diagnosis. Objectives: In instances such as assessing the health of breeding stock for export purposes where post-mortem testing is not an option, there is a demand for an ante-mortem test based on a matrix or body fluid that would permit easy access and repeated sampling. Urine and urine based analyses would meet these requirements. 相似文献913.
Pyruvate dehydrogenase (PDH) E1α is a key component in the PDH complex which catalyzes the oxidative decarboxylation of pyruvate
to acetyl-CoA. Defects in the gene coding for PDH E1α (PDHA1) are associated with a variety of clinical symptoms, often of
a severe character. In the present study, the segregation of three polymorphic CA repeats located in PDHA1 was followed in
the 40 CEPH reference pedigrees. Using these data, multipoint linkage analysis was carried out, refining the genetic location
of PDHA1. The 16-point map presented locates PDHA1 in an approximately 3-cM interval between DXS999 and DXS365 with odds of
more than 1000 : 1. From known physical localizations of the flanking marker loci, PDHA1 could be regionally assigned to Xp22.1-p22.2.
The information provided should be of value in clinical settings.
Received: 10 May 1996 相似文献