Evidence that cell surface localization of serine protease activity facilitates cleavage of the protease activated receptor CDCP1

Biol Chem. 2018 Sep 25;399(9):1091-1097. doi: 10.1515/hsz-2017-0308.

Abstract

The cellular receptor CUB domain containing protein 1 (CDCP1) is commonly elevated and functionally important in a range of cancers. CDCP1 is cleaved by serine proteases at adjacent sites, arginine 368 (R368) and lysine 369 (K369), which induces cell migration in vitro and metastasis in vivo. We demonstrate that membrane localization of serine protease activity increases efficacy of cleavage of CDCP1, and that both secreted and membrane anchored serine proteases can have distinct preferences for cleaving at CDCP1-R368 and CDCP1-K369. Approaches that disrupt membrane localization of CDCP1 cleaving serine proteases may interfere with the cancer promoting effects of CDCP1 proteolysis.

Keywords: CDCP1; CUB domain containing protein 1; cancer; serine protease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism*
  • Antigens, Neoplasm
  • Cell Adhesion Molecules / metabolism*
  • Cell Line, Tumor
  • Cell Membrane / enzymology*
  • Cell Movement
  • Humans
  • Kidney Neoplasms / metabolism*
  • Kidney Neoplasms / pathology
  • Neoplasm Proteins / metabolism*
  • Proteolysis
  • Receptors, Proteinase-Activated / metabolism*
  • Serine Proteases / metabolism*

Substances

  • Antigens, CD
  • Antigens, Neoplasm
  • CDCP1 protein, human
  • Cell Adhesion Molecules
  • Neoplasm Proteins
  • Receptors, Proteinase-Activated
  • Serine Proteases