The Evolution of IL6-IL6R-JAK-STAT Signaling Pathway in Metazoan.

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Main Authors: Yu, Hong, Chang, Renle, Wang, Houyou, He, Muchun, Sun, Jiejie, Song, Linsheng
Format: Artículo científico
Language:en
Published: Biology 2026
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author Yu, Hong
Chang, Renle
Wang, Houyou
He, Muchun
Sun, Jiejie
Song, Linsheng
author_facet Yu, Hong
Chang, Renle
Wang, Houyou
He, Muchun
Sun, Jiejie
Song, Linsheng
Yu, Hong
Chang, Renle
Wang, Houyou
He, Muchun
Sun, Jiejie
Song, Linsheng
collection PubMed - marine biology
contents The Evolution of IL6-IL6R-JAK-STAT Signaling Pathway in Metazoan. Yu, Hong Chang, Renle Wang, Houyou He, Muchun Sun, Jiejie Song, Linsheng The Interleukin-6 (IL6)-Interleukin-6 receptor (IL6R)-Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway plays a crucial role in innate immunity by inducing the production of various immune effectors. However, its stepwise evolutionary assembly across metazoans remains incompletely characterized. This study systematically screened 18 metazoan phyla or subphyla for the presence of IL6 family cytokines, their receptors, JAKs, and STATs. Phylogenetic relationships were constructed using Neighbor-Joining methods, and domain architectures were predicted via SMART. IL6 was found only in vertebrates, whereas IL6R could be traced to Mollusca. JAK and STAT appeared early in Porifera. IL6R, JAK1/2, STAT1 and STAT5A/B first co-existed in Mollusca. The IL-6 co-receptor gp130 was detected in fish, but was not reliably detected in available reptiles' and birds' genomes. The IL6-IL6R-JAK-STAT pathway was assembled incrementally: JAK and STAT were first detected in Porifera, IL6R was added in Mollusca to form the IL6R-JAK-STAT module, and finally, most IL6 family cytokines were present in vertebrates (fish). These findings might provide a pre-existing molecular framework that facilitated the subsequent evolution of the complete pathway in vertebrates. Collectively, this study provides a comprehensive evolutionary framework for the stepwise assembly of the IL6-IL6R-JAK-STAT signaling pathway across metazoans.
format Artículo científico
id pubmed_42187713
institution PubMed
language en
publishDate 2026
publisher Biology
record_format pubmed
spellingShingle The Evolution of IL6-IL6R-JAK-STAT Signaling Pathway in Metazoan.
Yu, Hong
Chang, Renle
Wang, Houyou
He, Muchun
Sun, Jiejie
Song, Linsheng
The Evolution of IL6-IL6R-JAK-STAT Signaling Pathway in Metazoan. Yu, Hong Chang, Renle Wang, Houyou He, Muchun Sun, Jiejie Song, Linsheng The Interleukin-6 (IL6)-Interleukin-6 receptor (IL6R)-Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway plays a crucial role in innate immunity by inducing the production of various immune effectors. However, its stepwise evolutionary assembly across metazoans remains incompletely characterized. This study systematically screened 18 metazoan phyla or subphyla for the presence of IL6 family cytokines, their receptors, JAKs, and STATs. Phylogenetic relationships were constructed using Neighbor-Joining methods, and domain architectures were predicted via SMART. IL6 was found only in vertebrates, whereas IL6R could be traced to Mollusca. JAK and STAT appeared early in Porifera. IL6R, JAK1/2, STAT1 and STAT5A/B first co-existed in Mollusca. The IL-6 co-receptor gp130 was detected in fish, but was not reliably detected in available reptiles' and birds' genomes. The IL6-IL6R-JAK-STAT pathway was assembled incrementally: JAK and STAT were first detected in Porifera, IL6R was added in Mollusca to form the IL6R-JAK-STAT module, and finally, most IL6 family cytokines were present in vertebrates (fish). These findings might provide a pre-existing molecular framework that facilitated the subsequent evolution of the complete pathway in vertebrates. Collectively, this study provides a comprehensive evolutionary framework for the stepwise assembly of the IL6-IL6R-JAK-STAT signaling pathway across metazoans.
title The Evolution of IL6-IL6R-JAK-STAT Signaling Pathway in Metazoan.
url https://pubmed.ncbi.nlm.nih.gov/42187713/