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Interaction of the Human Prostacyclin Receptor and the NHERF4 Family member Intestinal and Kidney Enriched PDZ Protein (IKEPP)
Date Issued
2012-10
Date Available
2012-10-16T15:04:48Z
Abstract
Prostacyclin and its I Prostanoid receptor, the IP, play central roles in haemostasis and in re-endothelialization in response to vascular injury. Herein, Intestinal and Kidney Enriched PDZ Protein (IKEPP) was identified as an interactant of the human (h) IP mediated through binding of PDZ domain 1 (PDZD1) and, to a lesser extent, PDZD2 of IKEPP to a carboxyl-terminal Class I ‘PDZ ligand’ within the hIP. While the interaction is constitutive, agonist-activation of the hIP leads to cAMP-dependent protein kinase (PK) A and PKC- phosphorylation of IKEPP, coinciding with its increased interaction with the hIP. Ectopic expression of IKEPP increases functional expression of the hIP, enhancing its ligand binding and agonist-induced cAMP generation. Originally thought to be restricted to renal and gastrointestinal tissues, herein, IKEPP was also found to be expressed in vascular endothelial cells where it co-localizes and complexes with the hIP. Furthermore, siRNA-disruption of IKEPP expression impaired hIP-induced endothelial cell migration and in vitro angiogenesis, revealing the functional importance of the IKEPP:IP interaction within the vascular endothelium. Identification of IKEPP as a functional interactant of the IP reveals novel mechanistic insights into the role of these proteins within the vasculature and, potentially, in other systems where they are co-expressed.
Sponsorship
Science Foundation Ireland
Type of Material
Journal Article
Publisher
Elsevier
Journal
Biochemica et Biophysica Acta
Volume
1823
Issue
10
Start Page
1998
End Page
2012
Copyright (Published Version)
2012 Elsevier B.V
Subject – LCSH
Prostacyclin--Receptors
Proteins
Phosphorylation
Language
English
Status of Item
Peer reviewed
This item is made available under a Creative Commons License
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Name
IKEPP hIP Ms BBA MCR 23rdAug2012incSupp.pdf
Description
Main Article including Supplemental Data
Size
10.15 MB
Format
Owning collection
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