Table 2.
Known substrates processed by CD26/DPP4 out of the immune system
| Substrate name and family | N-terminal sequence | Effect of DPP4 processing | In vitro/in vivo evidence | Reference |
|---|---|---|---|---|
| β-Casomorphins (neuropeptide) | Tyr-Pro▼Phe | Inhibitory | Yes/yes | [10, 82, 167] |
| BNP (natriuretic peptide) | Ser-Pro▼Lys |
Inhibitory Change in receptor preference |
Yes/yes | [82, 248] |
| Bradykinin (vasoactive) | Arg-Pro▼Pro |
Inhibitory Change in receptor preference |
Yes/yes | [10, 82, 167] |
| Endomorphins (neuropeptide) | Tyr-Pro▼Phe |
Inhibitory Change in receptor preference |
Yes/yes | [10, 41, 82, 167] |
| Enterostatin (gastrointestinal hormone) | Val-Pro▼Asp | Inhibitory | Yes/yes | [10, 41, 167] |
| GIP (incretin) | Tyr-Ala▼Glu | Inhibitory | Yes/yes | [10, 41, 82, 165, 167] |
| GLP: GLP-1 (7-36) amide, GLP-1 (7-37)b and GLP-2 (incretin) |
His-Ala▼Glu (GLP-1) His-Ala▼Asp (GLP-2) |
Inhibitory | Yes/yes | [10, 41, 82, 165, 167] |
| Glucagon (gastrointestinal hormone)a | His-Ser▼Gln | Inhibitory | Yes/yes | [82, 167] |
| GRH: GRH (1-29) and GRH (1-44) (hypothalamic hormone) | Tyr-Ala▼Asp | Inhibitory | Yes/no | [10] |
| GRP (bombesin family hormone) | Val-Pro▼Leu | Not known | Yes/yes | [82] |
| NPY (neuropeptide) | Tyr-Pro▼Ser |
Receptor Y1 Inactivation Change in receptor preference |
Yes/yes | [10, 41, 82, 167] |
| PACAP (PACAP27 and PACAP38)a | His-Ser▼Asp | Probably inhibitory | Yes/yes | [82, 249] |
| Peptide YY (pancreatic peptide) | Tyr-Pro▼Ile |
Receptor Y1 Inactivation Change in receptor preference |
Yes/yes | [10, 41, 82, 167] |
| Substance P (neuropeptide) | Arg-Pro▼Lys |
Inhibitory Questionable |
Yes/yes | [10, 41, 82, 167] |
| VIP peptides (VIP, PHV42, PHM27) (vasoactive)a |
His-Ala▼Asp (PHV, PHM) His-Ser▼Asp (VIP) |
Probably inhibitory | Yes/yes | [10, 41, 82, 165, 167] |
BNP B-type natriuretic peptide, GIP glucagon inhibitory peptide, GLP glucagon-like peptide, GRH growth hormone-releasing hormone, GRP gastrin-releasing peptide, NPY neuropeptide Y, PCAP pituitary adenylate cyclase-activating polypeptide, VIP vasoactive intestinal peptide, PHV42 peptide histidin valin 42, PHM27 peptide histidin methionine 27
aGlucagon, PACAP and VIP have a Ser in position 2 and, with less efficiency than Pro or Ala, also can be a DPP4 potential substrate
bGLP-1 (7-36) amide and (7-37) are the active forms of GLP-1 and substrates of DPP4