Prolactin induces phosphorylation of Tyr694 of Stat5 (MGF), a prerequisite for DNA binding and induction of transcription.

Abstract

Mammary gland factor (MGF) is a transcription factor discovered initially in the mammary epithelial cells of lactating animals. It confers the lactogenic hormone response to the milk protein genes. We reported recently the isolation of the cDNA encoding MGF. MGF is a novel member of the cytokine‐regulated transcription factor gene family. Members of this gene family mediate interferon alpha/beta and interferon gamma induction of gene transcription, as well as the response to epidermal growth factor and interleukin‐6, and have been named signal transducers and activators of transcription (Stat). The name Stat5 has been assigned to MGF. We studied the mechanisms involved in the prolactin activation of Stat5 in COS cells co‐transfected with cDNA encoding Stat5 and the prolactin receptor. Prolactin treatment of the transfected cells caused activation of Stat5 within 5‐10 min. This activation does not require ongoing protein synthesis. Tyrosine kinase inhibitors prevent Stat5 activation in transfected COS cells. Treatment of recombinant Stat5 with a tyrosine‐specific protein phosphatase in vitro abolishes its DNA binding activity. Prolactin stimulation of transfected cells induces Stat5 phosphorylation on tyrosine. Phosphorylation of in vitro transcribed and translated Stat5 with the Jak2 tyrosine kinase, but not with fyn, lyn or lck, confers DNA binding activity. The prolactin response of the beta‐casein milk protein gene promoter can be observed in COS cells transfected with cDNA vectors encoding Stat5 and the long form of the prolactin receptor. The short form of the prolactin receptor is unable to promote Stat5 phosphorylation and confer transcriptional induction in COS cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Human prolactin (hPRL) antagonists inhibit hPRL-activated signaling pathways involved in breast cancer cell proliferation

“…Treatment of T-47D cells with hPRL induces a rapid activation of STAT5b via phosphorylation of its Cterminal tyrosine (Gouilleux et al, 1994), which is time-(not shown) and dose-dependent (Figure 3a, left). As previously reported (Schaber et al, 1998), we failed to detect activation of Stat5a by PRL in T-47D (not shown).…”

Genetic variation and effects of candidate-gene polymorphisms on coagulation properties, curd firmness modeling and acidity in milk from Brown Swiss cows

“…STAT5A is activated by and mediates the responses of many cell ligands, including IL2, IL3, IL7 GM-CSF, erythropoietin, thrombopoietin and various growth hormones. STAT5A was first identified as a PRL-induced mammary gland factor (Gouilleux et al, 1994) and has been demonstrated to play critical roles in regulating apoptosis, promoting proliferation and enhancing cell cycle progression (Paukku and Silvennoinen, 2004). This gene was previously reported to have effects on the milk protein percentage, the milk fat percentage and embryonic survival (Khatib et al, 2008).…”

IL-3 dependent regulation of Bcl-xL gene expression by STAT5 in a bone marrow derived cell line

“…One of them involves the activation of STAT proteins (Signal Transducer and Activator of transcription) by cytokine receptorassociated tyrosine kinases of the Jak family Ihle, 1996). The STAT proteins are latent cytoplasmic transcription factors that become tyrosine phosphorylated after ligand binding (Shuai et al, 1993;Gouilleux et al, 1994). Activated STATs dimerize (homo-or hetero-dimerize), migrate into the nucleus, bind to speci®c DNA elements and activate the transcription of responsive genes.…”