endothelin maturation

Definition

Target type: biologicalprocess

The process leading to the attainment of the full functional capacity of endothelin by conversion of Big-endothelin substrate into mature endothelin. [GOC:BHF, GOC:rl]

Endothelin maturation is a complex process involving multiple steps, starting with the synthesis of preproendothelin, a large precursor protein. This precursor undergoes cleavage by a signal peptidase to generate proendothelin, which is then further processed by endothelin-converting enzyme (ECE) to yield the mature endothelin peptide. Endothelin exists in three isoforms, endothelin-1 (ET-1), endothelin-2 (ET-2), and endothelin-3 (ET-3), each with distinct amino acid sequences but sharing a common structural motif.

The process begins with the translation of endothelin mRNA, which encodes the preproendothelin protein. This precursor contains an N-terminal signal peptide that directs the protein to the endoplasmic reticulum (ER). Within the ER lumen, the signal peptide is cleaved by a signal peptidase, generating proendothelin. Proendothelin is further processed by ECE, a transmembrane enzyme located in the Golgi apparatus. ECE cleaves a specific peptide bond within proendothelin, resulting in the release of the mature endothelin peptide.

The maturation process is tightly regulated, and several factors can influence the production of endothelin. For example, angiotensin II, a vasoconstrictor, stimulates endothelin synthesis, while nitric oxide has an inhibitory effect. This intricate regulation ensures that endothelin levels remain within a physiological range, contributing to the maintenance of vascular tone and blood pressure.

Mature endothelin peptides exert their biological effects through binding to specific G protein-coupled receptors, known as endothelin receptors. These receptors are widely expressed in various tissues and cells, including vascular smooth muscle cells, endothelial cells, and the heart. Upon binding to its receptor, endothelin activates downstream signaling pathways, leading to vasoconstriction, smooth muscle contraction, and other physiological responses.

In summary, endothelin maturation is a multi-step process involving the cleavage of a precursor protein, proendothelin, by specific enzymes. This process is tightly regulated and results in the production of bioactive endothelin peptides that play crucial roles in various physiological processes.'
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Proteins (1)

Compounds (8)