Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The carboxyl-terminal cytoplasmic domain of the angiotensin II type 1 (AT1) receptor has recently been shown to interact with several classes of cytoplasmic proteins that regulate different aspects of AT1 receptor physiology. Employing yeast two-hybrid screening of a mouse kidney cDNA library with the carboxyl-terminal cytoplasmic domain of the murine AT1a receptor as a bait, we have isolated a novel protein with a predicted molecular mass of 18 kDa, which we have named ATRAP (for AT1 receptor-associated protein). ATRAP interacts specifically with the carboxyl-terminal domain of the AT1a receptor but not with those of angiotensin II type 2 (AT2), m3 muscarinic acetylcholine, bradykinin B2, endothelin B, and beta2-adrenergic receptors. The mRNA of ATRAP was abundantly expressed in kidney, heart, and testis but was poorly expressed in lung, liver, spleen, and brain. The ATRAP-AT1a receptor association was confirmed by affinity chromatography, by specific co-immunoprecipitation of the two proteins, and by fluorescence microscopy, showing co-localization of these proteins in intact cells. Overexpression of ATRAP in COS-7 cells caused a marked inhibition of AT1a receptor-mediated activation of phospholipase C without affecting m3 receptor-mediated activation. In conclusion, we have isolated a novel protein that interacts specifically with the carboxyl-terminal cytoplasmic domain of the AT1a receptor and affects AT1a receptor signaling.
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PMID:Cloning and characterization of ATRAP, a novel protein that interacts with the angiotensin II type 1 receptor. 1035 57

Hypertension is associated with vascular changes characterised by remodelling, endothelial dysfunction and hyperreactivity. Cellular processes underlying these perturbations include altered vascular smooth muscle cell growth and apoptosis, fibrosis, hypercontractility and calcification. Inflammation, associated with macrophage infiltration and increased expression of redox-sensitive pro-inflammatory genes, also contributes to vascular remodelling. Many of these features occur with ageing, and the vascular phenotype in hypertension is considered a phenomenon of 'premature vascular ageing'. Among the many factors involved in the hypertensive vascular phenotype, angiotensin II (Ang II) is especially important. Ang II, previously thought to be the sole effector of the renin-angiotensin system (RAS), is converted to smaller peptides [Ang III, Ang IV, Ang-(1-7)] that are biologically active in the vascular system. Another new component of the RAS is the (pro)renin receptor, which signals through Ang-II-independent mechanisms and might influence vascular function. Ang II mediates effects through complex signalling pathways on binding to its G-protein-coupled receptors (GPCRs) AT1R and AT2R. These receptors are regulated by the GPCR-interacting proteins ATRAP, ARAP1 and ATIP. AT1R activation induces effects through the phospholipase C pathway, mitogen-activated protein kinases, tyrosine kinases/phosphatases, RhoA/Rhokinase and NAD(P)H-oxidase-derived reactive oxygen species. Here we focus on recent developments and new research trends related to Ang II and the RAS and involvement in the hypertensive vascular phenotype.
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PMID:Angiotensin II and the vascular phenotype in hypertension. 2145 Jan 23