Document Type

Article

Publication Date

1-27-2026

Comments

This article is the author’s final published version in Cell reports, Volume 45, Issue 1, 2026, Article number 116703.

The published version is available at https://doi.org/10.1016/j.celrep.2025.116703. Copyright © 2025 The Author(s).

 

Abstract

Janus kinases 1 and 2 and STAT transcription factors are critical signaling nodes for numerous growth factors. In the mammary gland, JAK2 and STAT5a/b are essential for alveolar cell differentiation and lactation, but little is known about the cooperative roles of JAKs and STATs before pregnancy. We examined female mice conditionally deficient in JAK1/2 and discovered that both kinases jointly regulate epithelial cell proliferation and ductal morphogenesis. To assess the role of downstream STATs, we generated genetic models co-deficient in STAT3/5a/5b with or without STAT1 or JAK1. Although loss of STAT3/5a/5b leads to a JAK1-dependent upregulation of STAT1, the formation of mammary ducts is unaffected by the lack of expression and activation of all seven STAT proteins. Additionally, STAT deficiency impairs the cytokine-induced autophosphorylation of JAK1/2. These findings suggest that mammary duct development is orchestrated by STAT-independent signaling mechanisms of JAK1 and JAK2, potentially beyond their roles as tyrosine kinases.

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Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Language

English

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