Epithin/PRSS14 proteolytically regulates angiopoietin receptor Tie2 during transendothelial migration

Chungho Kim, Hyo Seon Lee, Deokjae Lee, Sang Don Lee, Eun Gyung Cho, Soo Jung Yang, Sang Bum Kim, Dongeun Park, Moon Gyo Kim

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Epithin/PRSS14, a type II transmembrane serine protease, is involved in normal epithelial development and tumor progression. Here we report, as an interacting substrate of epithin, a receptor tyrosine kinase Tie2 that is well known for important roles in the vessel stability. Epithin interacts with and degrades the Tie2 extracellular portion that contains the ligand-binding domain. Epithin is located in the neighbor of Tie2-expressing vessels in normal tissue. Furthermore, epithin can cleave and degrade Tie2 not only in the same cell but also from neighboring cells nearby, resulting in the degradation of the Tie2 ectodomain. The remaining Tie2 fragment was highly phosphorylated and was able to recruit a downstream effector, phosphatidylinositol 3-kinase. Knocking down epithin expression using short hairpin RNA in thymoma cell severely impaired the migration through endothelial cells that show the actin rearrangement during the process. The diminution of epithin protein expression in 4T1 breast cancer cells caused the significant decrease in the number of transendothelial migrating cells in vitro as well as in those of metastasizing tumor nodules in vivo, Therefore, we propose that epithin, which regulates endothelial Tie2 functions, plays a critical role in the fine tuning of transendothelial migration for normal and cancer cells.

Original languageEnglish
Pages (from-to)1415-1424
Number of pages10
JournalBlood
Volume117
Issue number4
DOIs
Publication statusPublished - 2011 Jan 27
Externally publishedYes

Fingerprint

TIE-2 Receptor
Angiopoietins
Transendothelial and Transepithelial Migration
Tumors
Cells
Phosphatidylinositol 3-Kinase
Endothelial cells
Receptor Protein-Tyrosine Kinases
Serine Proteases
Small Interfering RNA
Actins
Tuning
Tissue
Ligands
Degradation
Substrates
Neoplasms
Proteins
Thymoma
Endothelial Cells

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Kim, C., Lee, H. S., Lee, D., Lee, S. D., Cho, E. G., Yang, S. J., ... Kim, M. G. (2011). Epithin/PRSS14 proteolytically regulates angiopoietin receptor Tie2 during transendothelial migration. Blood, 117(4), 1415-1424. https://doi.org/10.1182/blood-2010-03-275289

Epithin/PRSS14 proteolytically regulates angiopoietin receptor Tie2 during transendothelial migration. / Kim, Chungho; Lee, Hyo Seon; Lee, Deokjae; Lee, Sang Don; Cho, Eun Gyung; Yang, Soo Jung; Kim, Sang Bum; Park, Dongeun; Kim, Moon Gyo.

In: Blood, Vol. 117, No. 4, 27.01.2011, p. 1415-1424.

Research output: Contribution to journalArticle

Kim, C, Lee, HS, Lee, D, Lee, SD, Cho, EG, Yang, SJ, Kim, SB, Park, D & Kim, MG 2011, 'Epithin/PRSS14 proteolytically regulates angiopoietin receptor Tie2 during transendothelial migration', Blood, vol. 117, no. 4, pp. 1415-1424. https://doi.org/10.1182/blood-2010-03-275289
Kim, Chungho ; Lee, Hyo Seon ; Lee, Deokjae ; Lee, Sang Don ; Cho, Eun Gyung ; Yang, Soo Jung ; Kim, Sang Bum ; Park, Dongeun ; Kim, Moon Gyo. / Epithin/PRSS14 proteolytically regulates angiopoietin receptor Tie2 during transendothelial migration. In: Blood. 2011 ; Vol. 117, No. 4. pp. 1415-1424.
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