MFGE8 inhibits insulin signaling through PTP1B.

ABSTRACT: The role of integrins in regulating insulin signaling is incompletely understood. We have previously shown that binding of the integrin ligand milk fat globule epidermal growth factor like 8 (MFGE8) to the αvβ5 integrin promotes termination of insulin receptor signaling in mice. Upon ligation of MFGE8, β5 complexes with the insulin receptor beta (IRβ) in skeletal muscle resulting in dephosphorylation of IRβ and reduction of insulin-stimulated glucose uptake. Here we investigate the mechanism by which the interaction between β5 and IRβ impacts IRβ phosphorylation status. We show that β5 blockade inhibits and MFGE8 promotes PTP1B binding to and dephosphorylation of IRβ resulting in reduced or increased insulin-stimulated myotube glucose uptake respectively. The β5-PTP1B complex is recruited

SUBMITTER: Datta R 

PROVIDER: S-EPMC10312531 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature