The mechanism of IGPR-1 activation in endothelial cells
Embargo Date
2020-07-02
OA Version
Citation
Abstract
Disruption of the integrity of vascular endothelium plays an essential role in the
development and the progression of numerous human diseases, including
sepsis, atherosclerosis and others. A complex array of transmembrane adhesive
proteins located in junctional structures, support endothelial integrity and control
vascular permeability. Furthermore, they are able to transmit intracellular signals
to coordinate various endothelial biological responses to insure normal vascular
function. Immunoglobulin-containing and proline rich receptor-1 (IGPR-1) is a
novel cell adhesion molecule that is involved in angiogenesis and in the
regulation of endothelial permeability. IGPR-1 is phosphorylated at Ser220,
which is required for its ability to mediate actin fibril reorganization. In this study,
we demonstrate that the phosphorylation of IGPR-1 at Ser220 is stimulated by
cell spreading and cell adhesion in porcine aortic endothelial (PAE) cells.
Blocking homophilic trans-dimerization of IGPR-1 by a blocking antibody inhibited
cell-density phosphorylation of IGPR-1. More importantly, phosphorylation of
IGPR-1 at Ser220 is increased in PAE cells under shear stress, which was
essential for IGPR-1-mediated endothelial cell alignment in response to shear
stress. Taken together, this study demonstrate that IGPR-1 activity is regulated
be endothelial cell spreading and density. And its activity plays an important role
in endothelial cell alignment in response to shear stress.
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Attribution 4.0 International