A novel insulin receptor-signaling platform and its link to insulin resistance and type 2 diabetes

A novel molecular organizational G-protein-coupled receptor (GPCR)-signaling platform potentiates neuraminidase-1 (Neu1) and matrix metalloproteinase-9 (MMP-9) cross talk on the cell surface that is essential for the activation of the insulin receptor β subunit (IRβ) tyrosine kinases. Notes: Insulin-binding receptor α subunits (IRα) potentiates the GPCR-signaling and MMP-9 activation to induce Neu1 sialidase. Activated MMP-9 is proposed to remove the elastin-binding protein (EBP) as part of the molecular multienzymatic complex that contains β-galactosidase/Neu1 and protective protein cathepsin A (PPCA). Activated Neu1 hydrolyzes α-2,3 sialyl residues of IRβ at the ectodomain to remove steric hindrance to facilitate IRβ subunits association and tyrosine kinase activation. Abbreviations: Pi3K, phosphatidylinositol 3-kinase; GTP, guanine triphosphate. Citation: Taken in part from Research and Reports in Biochemistry 2013:3 17-30. © 2013 Abdulkhalek et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted non-commercial use, provided the original work is properly cited.150