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| Item Type: | Article |
|---|---|
| Title: | Quantitative-proteomic comparison of alpha and beta cells to uncover novel targets for lineage reprogramming |
| Creators Name: | Choudhary, A., He, K.H., Mertins, P., Udeshi, N.D., Dančík, V., Fomina-Yadlin, D., Kubicek, S., Clemons, P.A., Schreiber, S.L., Carr, S.A. and Wagner, B.K. |
| Abstract: | Type-1 diabetes (T1D) is an autoimmune disease in which insulin-secreting pancreatic beta cells are destroyed by the immune system. An emerging strategy to regenerate beta-cell mass is through transdifferentiation of pancreatic alpha cells to beta cells. We previously reported two small molecules, BRD7389 and GW8510, that induce insulin expression in a mouse alpha cell line and provide a glimpse into potential intermediate cell states in beta-cell reprogramming from alpha cells. These small-molecule studies suggested that inhibition of kinases in particular may induce the expression of several beta-cell markers in alpha cells. To identify potential lineage reprogramming protein targets, we compared the transcriptome, proteome, and phosphoproteome of alpha cells, beta cells, and compound-treated alpha cells. Our phosphoproteomic analysis indicated that two kinases, BRSK1 and CAMKK2, exhibit decreased phosphorylation in beta cells compared to alpha cells, and in compound-treated alpha cells compared to DMSO-treated alpha cells. Knock-down of these kinases in alpha cells resulted in expression of key beta-cell markers. These results provide evidence that perturbation of the kinome may be important for lineage reprogramming of alpha cells to beta cells. |
| Keywords: | Calcium-Calmodulin-Dependent Protein Kinase Kinase, Cell Line, Glucagon-Secreting Cells, Insulin-Secreting Cells, Intracellular Signaling Peptides and Proteins, Phosphorylation, Protein-Serine-Threonine Kinases, Proteomics, Animals, Mice |
| Source: | PLoS ONE |
| ISSN: | 1932-6203 |
| Publisher: | Public Library of Science |
| Volume: | 9 |
| Number: | 4 |
| Page Range: | e95194 |
| Date: | 23 April 2014 |
| Official Publication: | https://doi.org/10.1371/journal.pone.0095194 |
| PubMed: | View item in PubMed |
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