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Pathway Description
Relaxin I Signaling Pathway
Homo sapiens
Signaling Pathway
Created: 2025-07-08
Last Updated: 2025-11-09
The Relaxin 1 signaling pathway starts when Relaxin 1 binds to its receptor, Relaxin receptor 1 (RXFP1), a G-protein–coupled receptor. Upon activation, RXFP1 stimulates multiple G-protein subunits including Gαs, Gαi3, Gαo, and Gβγ, which trigger several interconnected signaling cascades. Activation of Gαs leads to stimulation of adenylate cyclase 5, increasing cAMP levels and activating protein kinase A (PKA). PKA phosphorylates CREB and NFKBIA, promoting the nuclear translocation of phosphorylated CREB and the NF-κB (NFKB1–RELA) complex. Inside the nucleus, these transcription factors drive the expression of VEGF and inducible nitric oxide synthase (iNOS), which mediate angiogenesis and nitric oxide (NO) production.At the same time, Gβγ subunits activate PI3K, leading to the conversion of PIP2 to PIP3 and activation of AKT, which phosphorylates endothelial nitric oxide synthase (eNOS) to further enhance NO generation. In parallel, ERK1/2 activation stimulates transcription factor Jun, promoting MMP-2/9 expression involved in extracellular matrix remodeling. Through these coordinated pathways—cAMP/PKA–CREB, NF-κB, PI3K/AKT–eNOS, and ERK/JUN–MMP—the Relaxin 1 pathway regulates nitric oxide synthesis, vascular relaxation, angiogenesis, and tissue remodeling, supporting cardiovascular function, reproductive physiology, and tissue repair in humans.
References
Relaxin I Signaling Pathway References
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