Downregulation of Signaling-active IGF-1 by Dipeptidyl Peptidase IV (DPP-IV).

Abstract

Functioning as an extracellular protease, dipeptidyl peptidase IV (DPP-IV) preferentially cleaves the peptide bond after the penultimate proline residue. We report here that DPP-IV cleaves the first two amino acids from insulin-like growth factor 1 (IGF-1), revealed by mass spectrometry. The kinetic parameters of the proteolytic cleavage indicate that this reaction is physiologically relevant. Interestingly, truncated IGF-1 is less potent than the full-length protein in activating the IGF-1R, but binds more readily to IGF-binding protein 3 (IGFBP3). Quantitative RT-PCR showed that the level of DPP-IV mRNA is dramatically lower in lung squamous cell carcinoma tissues than in adjacent nonneoplastic lung tissues. However, this reduction was not observed in lung adenocarcinoma tissues. Our study suggests a possible link between IGF-1 and DPP-IV in cancer development in a specific tumor niche. A DPP-IV-related pathway may be important in mitigating IGF-1 signaling. Consequently, a robust IGF signaling pathway may accelerate early carcinogenesis in environments lacking DPP-IV.

• Authors: Ching-Ting Lin, Hsiang-Yun Tang, Yu-San Han, Hui-Ping Liu, Shiu-Feng Huang, Chia-Hui Chien, John Shyy, Jeng-Jian Chiu, Xin Chen
• Journal: International journal of biomedical science : IJBS (Int J Biomed Sci) Vol. 6 Issue 4 Pg. 301-9 (Dec 2010) ISSN: 1550-9702 [Print] United States
• PMID: 23675206 (Publication Type: Journal Article)