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

doi:10.1016/j.celrep.2025.116703

STAT-independent functions of Janus kinases 1 and 2 are obligatory for the postnatal development of mammary epithelial ducts

Title (eng)

STAT-independent functions of Janus kinases 1 and 2 are obligatory for the postnatal development of mammary epithelial ducts

Author

Rayane Dennaoui

Madison N. Wicker

Carson Moen

Michaela Schlederer

Kerry Vistisen

Aleata A. Triplett

Thomas Rülicke

University of Veterinary Medicine Vienna

Hallgeir Rui

Lukas Kenner

University of Veterinary Medicine Vienna

Emilio Casanova

Kay-Uwe Wagner

Abstract (eng)

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.

Keywords (eng)

Signal TransductionJanus Tyrosine KinasesKAK1JAK2STAT ProteinsGene TargetingConditional KnockoutMammary Gland DevelopementProtein-tyrosine KinaseMorphogenesisGrowth And DevelopmentFemaleDNA-binding ProteinsCre Recombinase

Type (eng)

journal article

Language

[eng]

Persistent identifier

https://phaidra.vetmeduni.ac.at/o:5279

DOI

10.1016/j.celrep.2025.116703

Is in series

Title (eng)

Cell Reports

Volume