Interaction of the Human Prostacyclin Receptor and the NHERF4 Family member Intestinal and Kidney Enriched PDZ Protein (IKEPP)

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Title: Interaction of the Human Prostacyclin Receptor and the NHERF4 Family member Intestinal and Kidney Enriched PDZ Protein (IKEPP)
Authors: Reid, Helen M.
Turner, Elizebeth C.
Mulvaney, Eamon P.
Hyland, Paula B.
McLean, Caitriona
Kinsella, B. Therese
Permanent link: http://hdl.handle.net/10197/3873
Date: Oct-2012
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.
Funding Details: 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
Keywords: Prostacyclin receptorIKEPPInteractionPhosphorylationNHERFGPCR
Subject LCSH: Prostacyclin--Receptors
Proteins
Phosphorylation
DOI: 10.1016/j.bbamcr.2012.07.015
Language: en
Status of Item: Peer reviewed
Appears in Collections:Biomolecular and Biomedical Science Research Collection

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