Apoptosis

, Volume 18, Issue 9, pp 1120–1131

Phosphorylation and nuclear translocation of integrin β4 induced by a chemical small molecule contribute to apoptosis in vascular endothelial cells

  • Di Ge
  • Xiangqian Kong
  • Weiyong Liu
  • Jing Zhao
  • Le Su
  • Shangli Zhang
  • Yun Zhang
  • Baoxiang Zhao
  • Junying Miao
Original Paper

DOI: 10.1007/s10495-013-0860-4

Cite this article as:
Ge, D., Kong, X., Liu, W. et al. Apoptosis (2013) 18: 1120. doi:10.1007/s10495-013-0860-4
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Abstract

Integrin β4 and its Y-1494 phosphorylation play an important role in cell signaling. We found a small molecule, ethyl1-(3-(4-chlorophenoxy)-2-hydroxypropyl)-3-(4-chlorophenyl)-1H-pyrazole-5-carboxylate (ECPC), that could elevate the levels of KIT ligand (KITLG), interleukin 8 (IL-8), prostaglandin-endoperoxide synthase 2 (PTGS2) and activating transcription factor 3 (ATF3) and promote apoptosis in vascular endothelial cells (VECs) through integrin β4. We investigated the underlying mechanism of integrin β4 participating in this process. ECPC treatment increased the phosphorylation of Y-1494 in the integrin β4 cytoplasmic domain via a well-known receptor tyrosine kinase, fibroblast growth factor receptor 1 (FGFR1), and integrin β4 translocated from the cytoplasm to nucleus. With suppression of Y-1494 phosphorylation by FGF-2 or siRNA of FGFR1, ECPC failed to promote integrin β4 nuclear translocation and could not increase the expression of KITLG, IL-8, PTGS2 or ATF3. Y-1494 phosphorylation and nuclear translocation of integrin β4 may be important during ECPC-induced apoptosis in VECs.

Keywords

Apoptosis Fibroblast growth factor receptor 1 Integrin β4 Integrin β4 phosphorylation Integrin β4 nucleus translocation Vascular endothelial cell 

Abbreviations

ECPC

Ethyl1-(3-(4-chlorophenoxy)-2-hydroxypropyl)-3-(4-chlorophenyl)-1H-pyrazole-5-carboxylate

VEC

Vascular endothelial cell

HUVECs

Human umbilical vein endothelial cells

IL-8

Interleukin 8

RNAi

RNA interference

siRNA

Small interfering RNA

FBS

Fetal bovine serum

FGF-2

Fibroblast growth factor-2

FGFR1

Fibroblast growth factor receptor 1

RTK

Receptor tyrosine kinase

PTGS2

Prostaglandin-endoperoxide synthase 2

ATF3

Activating transcription factor 3

EGFR

Epidermal growth factor receptor

DMSO

Dimethyl sulfoxide

Supplementary material

10495_2013_860_MOESM1_ESM.doc (33 kb)
Supplementary material 1 (DOC 33 kb)

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Di Ge
    • 1
  • Xiangqian Kong
    • 1
  • Weiyong Liu
    • 2
  • Jing Zhao
    • 1
  • Le Su
    • 1
  • Shangli Zhang
    • 1
  • Yun Zhang
    • 3
  • Baoxiang Zhao
    • 2
  • Junying Miao
    • 1
    • 3
  1. 1.Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life ScienceShandong UniversityJinanChina
  2. 2.Institute of Organic Chemistry, School of Chemistry and Chemical EngineeringShandong UniversityJinanChina
  3. 3.The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of HealthShandong University Qilu HospitalJinanChina

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