Transglutaminase 2-mediated serotonylation in pulmonary hypertension

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-li...

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Bibliographic Details
Published in:American journal of physiology. Lung cellular and molecular physiology 2014-02, Vol.306 (4), p.L309-L315
Main Authors: Penumatsa, K C, Fanburg, B L
Format: Article
Language:English
Subjects:
Animals
Calcium - physiology
Enzyme Activation
Enzymes
Familial Primary Pulmonary Hypertension
GTP-Binding Proteins
Humans
Hypertension, Pulmonary - enzymology
Hypertension, Pulmonary - physiopathology
Metabolism
Protein Processing, Post-Translational
Proteins
Pulmonary hypertension
Review
Rodents
Serotonin
Serotonin - metabolism
Signal Transduction
Transglutaminases - physiology
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Summary: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.
ISSN:1040-0605
1522-1504
DOI:10.1152/ajplung.00321.2013