Interaction of the human prostacyclin receptor with the PDZ adapter protein PDZK : role in endothelial cell migration and angiogenesis

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Title: Interaction of the human prostacyclin receptor with the PDZ adapter protein PDZK : role in endothelial cell migration and angiogenesis
Authors: Turner, Elizebeth C.
Mulvaney, Eamon P.
Reid, Helen M.
Kinsella, B. Therese
Permanent link: http://hdl.handle.net/10197/3148
Date: 8-Jun-2011
Abstract: Prostacyclin is increasingly implicated in re-endothelialization and angiogenesis but through largely unknown mechanisms. Herein, the HDL scavenger receptor class B, type 1 (SR-B1) adapter protein PDZ domain-containing protein 1 (PDZK1) was identified as an interactant of the human prostacyclin receptor (hIP) involving a Class I PDZ ligand at its carboxyl-terminus and PDZ domains 1, 3 and 4 of PDZK1. While the interaction is constitutive, it may be dynamically regulated following cicaprost-activation of the hIP through a mechanism involving cAMP-dependent protein kinase (PK)A-phosphorylation of PDZK1 at Ser505. While PDZK1 did not increase overall levels of the hIP, it increased its functional expression at the cell surface enhancing ligand binding and cicaprost-induced cAMP generation. Consistent with its role in re-endothelialization and angiogenesis, cicaprost-activation of the hIP increased endothelial cell migration and tube formation/in vitro angiogenesis, effects completely abrogated by the specific IP antagonist RO1138452. Furthermore, similar to HDL/SR-B1, siRNA-targeted disruption of PDZK1 abolished cicaprost-mediated endothelial responses but did not affect VEGF-responses. Considering the essential role played by prostacyclin throughout the cardiovascular system, identification of PDZK1 as a functional interactant of the hIP sheds significant mechanistic insights into the protective roles of these key players, and potentially HDL/SR-B1, within the vascular endothelium.
Funding Details: Science Foundation Ireland
Type of material: Journal Article
Publisher: American Society for Cell Biology
Copyright (published version): 2011 Turner et al. This article is distributed by The American Society for Cell Biology under license from the author(s).
Keywords: Prostacyclin receptor;PDZK1
Subject LCSH: Prostacyclin
Protein-protein interactions
Neovascularization
DOI: 10.1091/mbc.E11-04-0374
Language: en
Status of Item: Peer reviewed
Appears in Collections:Conway Institute Research Collection
Biomolecular and Biomedical Science Research Collection

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