eng Text journal article Open Access Elsevier © 2025 The Author(s). open access STAT-independent functions of Janus kinases 1 and 2 are obligatory for the postnatal development of mammary epithelial ducts Rayane Dennaoui Madison N. Wicker Carson Moen Michaela Schlederer Kerry Vistisen Aleata A. Triplett Thomas Rülicke Hallgeir Rui Lukas Kenner Emilio Casanova Kay-Uwe Wagner Signal Transduction Janus Tyrosine Kinases KAK1 JAK2 STAT Proteins Gene Targeting Conditional Knockout Mammary Gland Developement Protein-tyrosine Kinase Morphogenesis Growth And Development Female DNA-binding Proteins Cre Recombinase application/pdf Cell Reports Text Wissenschaftlicher Artikel doi:10.1016/j.celrep.2025.116703 http://creativecommons.org/licenses/by-nc/4.0/ Documento PDF Articolo scientifico 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. 2026 https://phaidra.vetmeduni.ac.at/o:5279