Kinetic study of the processing by dipeptidyl‐peptidase IV/CD26 of neuropeptides involved in pancreatic insulin secretion

FEBS Letters

De Meester, Ingrid¹  Van Damme, Jo²  Lambeir, Anne-Marie¹  Proost, Paul²  Durinx, Christine¹  Scharpé, Simon¹ 

[1] Laboratory of Medical Biochemistry, University of Antwerp (UIA), Universiteitsplein 1, B-2610 Antwerp, Belgium;Laboratory of Molecular Immunology, Rega Institute for Medical Research, University of Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium

关键词: Dipeptidyl-peptidase IV;    CD26;    Gastrin-releasing peptide;    Neuropeptide Y;    Vasoactive intestinal peptide;    Pituitary adenylyl cyclase-activating peptide;    DPP;    dipeptidyl-peptidase;    GIP;    glucose-dependent insulinotropic peptide;    GLP;    glucagon-like peptide;    GRP;    gastrin-releasing peptide;    NPY;    neuropeptide Y;    PACAP;    pituitary adenylyl cyclase-activating peptide;    VIP;    vasoactive intestinal peptide;   

DOI  :  10.1016/S0014-5793(01)02982-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Dipeptidyl-peptidase IV (DPPIV/CD26) metabolizes neuropeptides regulating insulin secretion. We studied the in vitro steady-state kinetics of DPPIV/CD26-mediated truncation of vasoactive intestinal peptide (VIP), pituitary adenylyl cyclase-activating peptide (PACAP27 and PACAP38), gastrin-releasing peptide (GRP) and neuropeptide Y (NPY). DPPIV/CD26 sequentially cleaves off two dipeptides of VIP, PACAP27, PACAP38 and GRP. GRP situates between the best DPPIV/CD26 substrates reported, comparable to NPY. Surprisingly, the C-terminal extension of PACAP38, distant from the scissile bond, improves both PACAP38 binding and turnover. Therefore, residues remote from the scissile bond can modulate DPPIV/CD26 substrate selectivity as well as residues flanking it.

【 授权许可】

Unknown