STAT-independent functions of Janus kinases 1 and 2 are obligatory for the postnatal development of mammary epithelial ductsShow others and affiliations
2026 (English)In: Cell Reports, ISSN 2639-1856, E-ISSN 2211-1247, Vol. 45, no 1, article id 116703
Article in journal (Refereed) Published
Abstract [en]
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.
Place, publisher, year, edition, pages
Elsevier, 2026. Vol. 45, no 1, article id 116703
Keywords [en]
conditional knockout, CP: cell biology, CP: developmental biology, Cre recombinase, DNA-binding proteins, female, gene targeting, growth and development, JAK1, JAK2, Janus tyrosine kinases, mammary gland development, morphogenesis, protein-tyrosine kinase, signal transduction, STAT proteins
National Category
Medical Biotechnology (Focus on Cell Biology, (incl. Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-249687DOI: 10.1016/j.celrep.2025.116703Scopus ID: 2-s2.0-105029044799OAI: oai:DiVA.org:umu-249687DiVA, id: diva2:2036842
2026-02-092026-02-092026-02-09Bibliographically approved