Connective tissue growth factor is a substrate of ADAM28

Satsuki Mochizuki, Rena Tanaka, Masayuki Shimoda, Junko Onuma, Yutaka Fujii, Hiromitsu Jinno, Yasunori Okada

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

ADAM28, a member of the ADAM (a disintegrin and metalloproteinase) gene family, is over-expressed by carcinoma cells and the expression correlates with carcinoma cell proliferation and progression in human lung and breast carcinomas. However, information about substrates of ADAM28 is limited. We screened interacting molecules of ADAM28 in human lung cDNA library by yeast two-hybrid system and identified connective tissue growth factor (CTGF). Binding of CTGF to proADAM28 was demonstrated by yeast two-hybrid assay and protein binding assay. ADAM28 cleaved CTGF in dose- and time-dependent manners at the Ala 181-Tyr 182 and Asp 191-Pro 192 bonds in the hinge region of the molecule. ADAM28 selectively digested CTGF in the complex of CTGF and vascular endothelial growth factor 165 (VEGF 165), releasing biologically active VEGF 165 from the complex. RT-PCR and immunohistochemical analyses demonstrated that ADAM28, CTGF and VEGF are commonly co-expressed in the breast carcinoma tissues. These data provide the first evidence that CTGF is a novel substrate of ADAM28 and suggest that ADAM28 may promote VEGF 165-induced angiogenesis in the breast carcinomas by the CTGF digestion in the CTGF/VEGF 165 complex.

Original languageEnglish
Pages (from-to)651-657
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume402
Issue number4
DOIs
Publication statusPublished - 2010 Nov 26

Keywords

  • A disintegrin and metalloproteinase
  • Angiogenesis
  • Connective tissue growth factor
  • Digestion
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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