January 04, 2013

Function characteristics of naturally occurring transglutaminase 2 mutant and early onset of type 2 diabetes.

Transglutaminase 2 (TG2) is a kind o enzyme and different biological function. Transamidation TG2 catalytic reaction, has intrinsic kinase activity, and ACTS as a g protein within the cell signal. TG2 (Tgm2) null mice blood glucose intolerance, damaged biology insulin secretion (GSIS). In addition, three naturally occurring missense mutation, gene in human TGM2 corresponding Met330Arg amino acid substitutions, Ile331Asn, Asn333Ser TG2 in protein, report and found to be related to the type 2 diabetes and early onset. However, their influence is still not fully understand TG2 function. In order to prove this point, we have again naturally occurring mutation site-directed mutagenesis TG2 use. In the INS - 1 e express Myc - TG2 mutant cells leads to reduce GSIS and cell excessive expression compared with wild type Myc - TG2 (WT - TG2). The biggest decrease was found in cell excessive express Ile331Asn - TG2 (32%), the second is Met330Arg - TG2 (20%), at least in the Asn333Ser - TG2 (7%). Enzyme analysis suggests that transamidation TG2 mutant damaged and kinase activity and WT - TG2 compared. Tests show the GTP binding TG2 mutant also changed the GTP binding ability, it is found that modulation response glucose stimulation. In general, these data show that naturally occurring mutations affecting the transamidation TG2, kinase, GTP binding TG2 function. Although reduce insulin secretion, because naturally occurring mutations, is due to TG2 detract from more than one biological function, it is transamidation TG2 function, it seems to be in the first stage is impaired, and GTP binding function will affect the second stage of insulin secretion.


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