Peptide-based sequestration of the adaptor protein Nck1 in pancreatic β cells enhances insulin biogenesis and protects against diabetogenic stresses.

ABSTRACT: One feature of diabetes is the failure of pancreatic β cells to produce insulin, but the molecular mechanisms leading to this failure remain unclear. Increasing evidence supports a role for protein kinase R-like endoplasmic reticulum kinase (PERK) in the development and function of healthy pancreatic β cells. Previously, our group identified the adaptor protein Nck1 as a negative regulator of PERK. Indeed, we demonstrated that Nck1, by directly binding PERK autophosphorylated on Tyr⁵⁶¹, limits PERK activation and signaling. Accordingly, we found that stable depletion of Nck1 in β cells promotes PERK activation and signaling, increases insulin biosynthesis, and improves cell viability in response to diabetes-related stresses. Herein, we explored the therapeutic potential of abrog

SUBMITTER: Kefalas G 

PROVIDER: S-EPMC6093234 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature