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Pathway Description
Prolactin signaling pathway
Homo sapiens
Signaling Pathway
Created: 2025-09-08
Last Updated: 2025-10-07
The prolactin signaling pathway in Homo sapiens begins when prolactin, secreted by the pituitary gland, binds to and activates prolactin receptor (PRLR) dimers on mammary epithelial cells. This triggers recruitment and phosphorylation of the tyrosine kinase JAK2, which in turn phosphorylates both the receptor and STAT5A. Activated STAT5A forms dimers that translocate to the nucleus, where they regulate transcription of key genes involved in lactation (such as β-casein), cell survival (BCL2), cell cycle progression (Cyclin D1), and negative feedback regulators (SOCS2, SOCS3, CISH, IRF1). In parallel, PRLR signaling activates the MAPK/ERK cascade through GRB2–SOS–RAS–RAF–MEK–ERK, promoting cell proliferation and differentiation. The receptor also engages the PI3K–AKT–mTOR pathway via IRS1, enhancing cell survival, metabolism, and protein synthesis. Together, these interconnected sub-pathways coordinate mammary gland development, lactation, and cellular homeostasis, while negative regulators such as SOCS proteins, PIAS, and phosphatases prevent overactivation of the pathway.
References
Prolactin signaling pathway References
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