Prolactin mediated intracellular signaling in mammary epithelial cells.
Prolactin binds to a member of the cytokine receptor superfamily. The cytoplasmic domain of the prolactin receptor (PrlR) displays no enzymatic activity yet prolactin treatment leads to the induction of protein tyrosine phosphorylation. PrlR is associated with JAK2, a protein tyrosine kinase whose activity is stimulated following receptor dimerization. JAK2 subsequently phosphorylates PrlR and other cellular proteins which are recruited to the activated receptor complex. Among the JAK2 substrates is the transcription factor Stat5 whose phosphorylation mediates the transcriptional activation of beta-casein gene expression. In this review we discuss the prolactin induced signaling pathways which mediate differentiation of the mammary gland.
Hynes
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NE
Friedrich Miescher Institute, Basel, Switzerland. hynes@fmi.ch
Cella
N
N
Wartmann
M
M
D000818:Animals; D001940:Breast / Q000166:cytology*; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000502:physiology; D004847:Epithelial Cells / Q000502:physiology; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D053614:Janus Kinase 2; D020935:MAP Kinase Signaling System; D008321:Mammary Glands, Animal / Q000166:cytology*; D008894:Milk Proteins; D011388:Prolactin / Q000502:physiology*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011518:Proto-Oncogene Proteins; D011981:Receptors, Prolactin / Q000502:physiology; D050799:STAT5 Transcription Factor; D015534:Trans-Activators / Q000502:physiology
D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008894:Milk Proteins; D011518:Proto-Oncogene Proteins; D011981:Receptors, Prolactin; D050799:STAT5 Transcription Factor; D015534:Trans-Activators; D011388:Prolactin; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases