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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Weber, A.E. J. Med. Chem. 47, 4135–4141 (2004).
Yates, N.A. et al. Int. J. Mass Spectrom. 259, 174–183 (2007).
Che, F.Y., Yuan, Q., Kalinina, E. & Fricker, L.D. J. Biol. Chem. 280, 4451–4461 (2005).
Rosenblum, J.S. & Kozarich, J.W. Curr. Opin. Chem. Biol. 7, 496–504 (2003).
Marguet, D. et al. Proc. Natl. Acad. Sci. USA 97, 6874–6879 (2000).
Venable, J.D., Dong, M.Q., Wohlschlegel, J., Dillin, A. & Yates, J.R. Nat. Methods 1, 39–45 (2004).
Leiting, B. et al. Biochem. J. 371, 525–532 (2003).
Deacon, C.F., Pridal, L., Klarskov, L., Olesen, M. & Holst, J.J. Am. J. Physiol. 271, E458–E464 (1996).
Villhauer, E.B. et al. J. Med. Chem. 46, 2774–2789 (2003).
Saghatelian, A. et al. Biochemistry 43, 14332–14339 (2004).
Tiruppathi, C. et al. J. Biol. Chem. 265, 1476–1483 (1990).
Medeiros, M.D. & Turner, A.J. Endocrinology 134, 2088–2094 (1994).
Erickson, R.H. et al. Dig. Dis. Sci. 34, 400–406 (1989).
Rangel, R. et al. Proc. Natl. Acad. Sci. USA 104, 4588–4593 (2007).
Marchio, S. et al. Cancer Cell 5, 151–162 (2004).
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.
Author information
Authors and Affiliations
Contributions
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.
Corresponding author
Supplementary information
Supplementary Text and Figures
Supplementary Figures 1–6, Supplementary Table 1 and Supplementary Methods (PDF 2616 kb)
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nchembio.126
This article is cited by
-
Phytohormone treatment induces generation of cryptic peptides with antimicrobial activity in the Moss Physcomitrella patens
BMC Plant Biology (2019)
-
The gut–renal axis: do incretin-based agents confer renoprotection in diabetes?
Nature Reviews Nephrology (2014)
-
The potential for renoprotection with incretin-based drugs
Kidney International (2014)
-
Determining target engagement in living systems
Nature Chemical Biology (2013)
-
Peptidomic discovery of short open reading frame–encoded peptides in human cells
Nature Chemical Biology (2013)