Interaction of the human prostacyclin receptor and the NHERF4 family member intestinal and kidney enriched PDZ protein (IKEPP).
Prostacyclin and its I prostanoid receptor, the IP, play central roles in hemostasis 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 (PDZ(D1)) and, to a ... lesser extent, PDZ(D2) 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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Cell Movement, Cyclic AMP-Dependent Protein Kinases, HEK293 Cells, Human Umbilical Vein Endothelial Cells, Humans, Kidney, Ligands, Models, Biological, Neoplasm Proteins, Neovascularization, Physiologic, Phosphoproteins, Protein Binding, Protein Kinase C, Protein Structure, Tertiary, Receptors, Prostaglandin, Signal Transduction, Sodium-Hydrogen Antiporter
Adaptor Proteins, Signal Transducing, Cell Movement, Cyclic AMP-Dependent Protein Kinases, HEK293 Cells, Human Umbilical Vein Endothelial Cells, Humans, Kidney, Ligands, Models, Biological, Neoplasm Proteins, Neovascularization, Physiologic, Phosphoproteins, Protein Binding, Protein Kinase C, Protein Structure, Tertiary, Receptors, Prostaglandin, Signal Transduction, Sodium-Hydrogen Antiporter
Biochim. Biophys. Acta
Date: Oct. 01, 2012
PubMed ID: 22884631
View in: Pubmed Google Scholar
Download Curated Data For This Publication
160315
Switch View:
- Interactions 3