| First Author | Nie J | Year | 2013 |
| Journal | Proc Natl Acad Sci U S A | Volume | 110 |
| Issue | 34 | Pages | 13857-62 |
| PubMed ID | 23922392 | Mgi Jnum | J:200755 |
| Mgi Id | MGI:5509236 | Doi | 10.1073/pnas.1307698110 |
| Citation | Nie J, et al. (2013) SAD-A kinase controls islet beta-cell size and function as a mediator of mTORC1 signaling. Proc Natl Acad Sci U S A 110(34):13857-62 |
| abstractText | The mammalian target of rapamycin (mTOR) plays an important role in controlling islet beta-cell function. However, the underlying molecular mechanisms remain poorly elucidated. Synapses of amphids defective kinase-A (SAD-A) is a 5' adenosine monophosphate-activated protein kinase-related protein kinase that is exclusively expressed in pancreas and brain. In this study, we investigated a role of the kinase in regulating pancreatic beta-cell morphology and function as a mediator of mTOR complex 1 (mTORC1) signaling. We show that global SAD-A deletion leads to defective glucose-stimulated insulin secretion and petite islets, which are reminiscent of the defects in mice with global deletion of ribosomal protein S6 kinase 1, a downstream target of mTORC1. Consistent with these findings, selective deletion of SAD-A in pancreas decreased islet beta-cell size, whereas SAD-A overexpression significantly increased the size of mouse insulinomas cell lines beta-cells. In direct support of SAD-A as a unique mediator of mTORC1 signaling in islet beta-cells, we demonstrate that glucose dramatically stimulated SAD-A protein translation in isolated mouse islets, which was potently inhibited by rapamycin, an inhibitor of mTORC1. Moreover, the 5'-untranslated region of SAD-A mRNA is highly structured and requires mTORC1 signaling for its translation initiation. Together, these findings identified SAD-A as a unique pancreas-specific effector protein of mTORC1 signaling. |
