, Volume 18, Issue 9, pp 1120-1131
Date: 16 May 2013

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

Rent the article at a discount

Rent now

* Final gross prices may vary according to local VAT.

Get Access

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.