TSC1-TSC2 complex on the crossroad of pancreatic β cell signaling. Role on cell proliferation, death and survival

Resumen

TSC1-TSC2 complex has emerged as a signal interaction core within the cell. This complex integrates both nutrient and growth factor signaling and is a critical negative regulator of mTORC1. mTORC1 signaling leads to increased protein biosynthesis, which is essential for cell proliferation. Other cellular events such as endoplasmic reticulum stress and authophagy are intimately linked with TSC/mTORC1 pathway and play an important role in pancreatic ß cell death or survival. We found that either insulin, glucose independent signaling or the energetic status of the cell are able to modulate TSC2 phosphorylation in pancreatic ß cell lines. To show the central role of TSC2 for these cells, we conducted siRNA-mediated TSC2 silencing. Downregulation of TSC2 leads to an increase in mTORC1/p70S6K signaling, this produces resistance to insulin action. However, specific expression of insulin receptor isoform A restored insulin signalling under these conditions. Moreover, we have explored other processes related to the TSC/mTORC1 pathway and their effect on cell death or survival