Transglutaminase 2-mediated Serotonylation in Pulmonary Hypertension

Overview

Journal Am J Physiol Lung Cell Mol Physiol

Publisher American Physiological Society

Specialties Cell Biology
Molecular Biology
Physiology
Pulmonary Medicine

Date 2013 Dec 31

PMID 24375797

Citations 25

Authors

K C Penumatsa

B L Fanburg

Affiliations

Soon will be listed here.

Abstract

The monoamine serotonin (5-HT) has been previously implicated in pulmonary arterial remodeling and is considered a potential therapeutic target for the disease pulmonary arterial hypertension (PAH). More recently, it has been recognized that the enzyme tissue transglutaminase (TG2) mediates cross-linking of proteins with 5-HT, a posttranslational process of monoaminylation known as "serotonylation." TG2 activity and serotonylation of protein participate in both smooth muscle proliferation and contraction produced by 5-HT. Indeed, markedly increased TG2 activity has now been identified in lung tissue of an experimental rodent model of pulmonary hypertension, and elevated serotonylation of fibronectin and the signaling molecule Rho, downstream products of transglutamidation, have been found in blood of patients with PAH. The basic mechanism by which TG2 is activated and the potential role(s) of serotonylated proteins in pulmonary hypertension remain a mystery. In the present review we have tried to address the current understanding of 5-HT metabolism in pulmonary hypertension and relate it to what is currently known about the evolving cellular process of serotonylation.

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