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By point-mutational and structural modelling, we have identified one amino acid in the juxtamembrane region of the ICD of the two receptors that determines substrate preference and plays a major role in differentiating IR and IGF1R action with respect to both signalling and gene expression

These putative direct targets include the mitochondria-localized isoform of glycerol-3-phosphate dehydrogenase (encoded by the GPD2 gene), the mitochondria-localized isoform of serine hydroxymethyltransferase (encoded by the SHMT2 gene), presenilin enhancer, gamma-secretase subunit (commonly identified as PEN2

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Second, due to the interdependent nature of the IPPS payment components, it is very difficult to precisely quantify the impact associated with each proposed change

Further, the in vivo significance of the identified modifications remains in many cases to be established