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The Effect of Mutating the PDZ domains within secreted PDZD2   Zee man, Winnie Wat

The Effect of Mutating the PDZ domains within secreted PDZD2

96 страниц. 2011 год.
LAP Lambert Academic Publishing
PDZ domains are one of the most common protein-protein interaction domains in human. PDZ domain containing 2 protein (PDZD2) contains 6 PDZ domains and is highly expressed in pancreatic beta cells. It undergoes cleavage in the endoplasmic reticulum to produce a secreted form PDZD2 (sPDZD2) which retains the last two PDZ domains of PDZD2. sPDZD2 is a candidate beta cell regulatory factor. In current study, two mutated forms of sPDZD2 were generated with alterations in the amino acid sequence within the carboxylate-binding loop of one of the two PDZ domains, either at the PDZ5 or at the PDZ6 domain. Current study revealed that both the PDZ5-mutated and PDZ6-mutated sPDZD2 proteins failed to exert the insulinotropic effect that the wildtype sPDZD2 had on INS-1E cells when added exogenously in the culture medium. Both mutant proteins also failed to rescue the silencing action of siRNA on the insulinotropic effect of endogenous PDZD2 in INS-1E cells. These results suggest that...
 
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