Abstract
Peptide metabolism is a complex process that involves many proteins working in concert. Mass spectrometry–based global peptide profiling of mice lacking dipeptidyl peptidase 4 (DPP4) identified endogenous DPP4 substrates and revealed an unrecognized pathway during proline peptide catabolism that interlinks aminopeptidase and DPP4 activities. Together, these studies elucidate specific aspects of DPP4-regulated metabolism and, more generally, highlight the utility of global peptide profiling for studying peptide metabolism in vivo.
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Acknowledgements
This work was supported by US National Institutes of Health grant 1DP2OD002374 (A.S.) and a Burroughs Wellcome Fund Career Award in the Biomedical Sciences (A.S.). The authors thank B.F. Cravatt III, D.R. Liu, D. Kahne and other members of the research group for helpful discussions.
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D.M.T. and A.S. conceived and designed the experiments. D.M.T., W.M.N., J.M.N. and W.S.L. carried out the mass spectrometry experiments and analyzed the data. D.M.T. carried out all the remaining experiments (in vitro DPP4 assays and brush border membrane experiments) and analyzed all the data. R.R., L.G.-R., R.P. and W.A. produced the Anpep−/− Enpep−/− mice. The manuscript was written by D.M.T. and A.S.
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Supplementary Figures 1–6, Supplementary Table 1 and Supplementary Methods (PDF 2616 kb)
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Tagore, D., Nolte, W., Neveu, J. et al. Peptidase substrates via global peptide profiling. Nat Chem Biol 5, 23–25 (2009). https://doi.org/10.1038/nchembio.126
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DOI: https://doi.org/10.1038/nchembio.126
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