Both 17 -estradiol and prolactin play important roles in the mammary gland, raising the possibility of functional cross-talk between the two signaling pathways. Here, we demonstrate that estrogen receptor(ER ) and (ER ) are both able to potentiate transcription from a Stat5-responsive promoter when activated by prolactin. Potentiation was observed not only in the presence of 17 estradiol, but a...

Signal transducer and activator of transcription 5A and 5B (STAT5A/5B) are encoded by closely related and chromosomally juxtaposed genes. Both proteins play a major role in normal hematopoiesis. STAT5A/B-deficient hematopoietic progenitors failed to repopulate the bone marrow in competitive repopulation assays and have a reduced ability to respond to early-acting cytokines such as interleukin (...

Janus kinases (JAKs) are cytoplasmic tyrosine kinases critical for signaling by growth hormone (GH) and many other ligands that bind to members of the cytokine receptor superfamily. SH2-Bbeta was previously identified as a JAK2-interacting protein that is tyrosyl phosphorylated in response to GH and other cytokines that activate JAK2. In this study, we examined whether SH2-Bbeta alters the acti...

In mice, the onset of parturition is triggered by a rapid decline in circulating progesterone. Progesterone withdrawal occurs as a result of functional luteolysis, which is characterized by an increase in the enzymatic activity of 20α-hydroxysteroid dehydrogenase (20α-HSD) in the corpus luteum and is mediated by the prostaglandin F2α (PGF2α) signaling. Here, we report that the genetic knockout ...

Polyunsaturated fatty acids, including docosahexaenoic acid (DHA, 22:6n-3), modulate immune responses and exert beneficial immunosuppressive effects, but the molecular mechanisms inhibiting T-cell activation are not yet elucidated. Lipid rafts have been shown to play an important role in the compartmentalization and modulation of cell signaling. We investigated the role of DHA in modulating the...

Polyunsaturated fatty acids (PUFAs) including docosahexaenoic acid (DHA; 22:6 n-3) modulate immune responses and exert beneficial immunosuppressive effects, but the molecular mechanisms inhibiting T cell activation are not yet elucidated. Lipid rafts have been shown to play an important role in the compartmentalization and modulation of cell signaling. We investigate the role of DHA in modulati...

3-Methylcholanthrene (MC) is a readily metabolized aryl hydrocarbon receptor (AHR) agonist. MC disrupts expression of mouse hepatic growth hormone (GH) signaling components and suppresses cytochrome P450 2D9 (Cyp2d9), a male-specific gene controlled by pulsatile GH via signal transducer and activator of transcription 5b (STAT5b). To determine if these effects of MC depend on hepatic microsomal ...

The transcription factors Signal Transducer and Activator of Transcription (STAT) 5A/B mediate prolactin-induced mammary development during pregnancy. However, it is not clear how the different processes, expansion and maturation of alveolar precursor cells and the differential induction of milk protein genes are regulated on a molecular level. We have used mouse genetics and genome-wide analys...

The signal transducer and activator of transcription 5 (Stat5) has been shown to cooperate with some nuclear receptors. However, an interaction has never been demonstrated with the androgen receptor (AR). Given that the PRL-inducible protein/gross cystic disease fluid-15 (PIP/GCDFP-15) is both a PRL-controlled and an androgen-controlled protein, we used its promoter region to investigate the po...

Gram negative sepsis with release of endotoxin is a frequent cause of cachexia that develops partly because of resistance to growth hormone (GH) with reduced IGF-1 expression. We set out to more fully characterize the mechanisms for the resistance and to determine whether in addition to a defect in the janus kinase 2 (JAK2)-signal transducer and activator of transcription (STAT) 5b pathway, req...