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

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dc.contributor.author Reid, Helen M.
dc.contributor.author Turner, Elizebeth C.
dc.contributor.author Mulvaney, Eamon P.
dc.contributor.author Hyland, Paula B.
dc.contributor.author McLean, Caitriona
dc.contributor.author Kinsella, B. Therese
dc.date.accessioned 2012-10-16T15:04:48Z
dc.date.available 2012-10-16T15:04:48Z
dc.date.copyright 2012 Elsevier B.V en
dc.date.issued 2012-10
dc.identifier.citation Biochemica et Biophysica Acta en
dc.identifier.uri http://hdl.handle.net/10197/3873
dc.description.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. en
dc.description.sponsorship Science Foundation Ireland en
dc.language.iso en en
dc.publisher Elsevier en
dc.rights This is the author’s version of a work that was accepted for publication in Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Biochimica et Biophysica Acta (BBA) - Molecular Cell Research (Volume 1823, Issue 10, October 2012, Pages 1998–2012) DOI:10.1016/j.bbamcr.2012.07.015 en
dc.subject Prostacyclin receptor en
dc.subject IKEPP en
dc.subject Interaction en
dc.subject Phosphorylation en
dc.subject NHERF en
dc.subject GPCR en
dc.subject.lcsh Prostacyclin--Receptors en
dc.subject.lcsh Proteins en
dc.subject.lcsh Phosphorylation en
dc.title Interaction of the Human Prostacyclin Receptor and the NHERF4 Family member Intestinal and Kidney Enriched PDZ Protein (IKEPP) en
dc.type Journal Article en
dc.internal.availability Full text available en
dc.status Peer reviewed en
dc.identifier.volume 1823 en
dc.identifier.issue 10 en
dc.identifier.startpage 1998 en
dc.identifier.endpage 2012 en
dc.identifier.doi 10.1016/j.bbamcr.2012.07.015
dc.neeo.contributor Reid|Helen M.|aut|
dc.neeo.contributor Turner|Elizebeth C.|aut|
dc.neeo.contributor Mulvaney|Eamon P.|aut|
dc.neeo.contributor Hyland|Paula B.|aut|
dc.neeo.contributor McLean|Caitriona|aut|
dc.neeo.contributor Kinsella|B. Therese|aut|
dc.description.admin DG - 10/10/12 en


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