STATs are proteins that serve the dual function of signal transducers and activators of transcription in cells exposed to signaling polypeptides. A variety of cytokines mediate the activation of Janus protein tyrosine kinases (Jaks). The Jaks then phosphorylate cellular substrates, including members of the signal transducers and activators of transcription (Stat) family of transcription factors. Hou et al. (1995) identified STAT5 as the protein most notably induced in response to T-cell activation with IL2. They hypothesized that STAT5 may govern the effects of IL2 during the immune response. They cloned the human STAT5 cDNA from an umbilical vein endothelial cell library and found that it encodes a 794-amino acid polypeptide with a predicted mass of approximately 90.5 kD.
NCBI Summary:
The protein encoded by this gene is a member of the STAT family of transcription factors. In response to cytokines and growth factors, STAT family members are phosphorylated by the receptor associated kinases, and then form homo- or heterodimers that translocate to the cell nucleus where they act as transcription activators. This protein is activated by, and mediates the responses of many cell ligands, such as IL2, IL3, IL7 GM-CSF, erythropoietin, thrombopoietin, and different growth hormones. Activation of this protein in myeloma and lymphoma associated with a TEL/JAK2 gene fusion is independent of cell stimulus and has been shown to be essential for the tumorigenesis. The mouse counterpart of this gene is found to induce the expression of BCL2L1/BCL-X(L), which suggests the antiapoptotic function of this gene in cells.
General function
Intracellular signaling cascade, Nucleic acid binding, DNA binding, Transcription factor
Comment
Cellular localization
Nuclear
Comment
Ovarian function
Luteinization
Comment
Alpha 2-Macroglobulin (alpha 2M) is expressed at high levels in the corpus luteum of pregnant rats in response to PRL and rat placental lactogens. To analyze the cellular signaling events stimulated by PRL, transient transfections of granulosa cells and electrophoretic mobility shift assays were done using the IL-6 response element (IL-6RE) of the alpha 2M promoter. PRL appears to activate detectable amounts of Stat 5 (and not Stat 3). and the initial induction of the alpha 2M gene by PRL in differentiated rat granulosa cells involves, at least in part, the activation of Stat 5 (Daje et al., 1996).
Expression regulated by
LH, Growth Factors/ cytokines, prolactin
Comment
Ruff et al. (1996) demonstrate that Stat 5, previously identified as a transcription factor activated by PRL in the mammary gland, is also activated by PRL in the ovaries of pseudopregnant rats. Intraperitoneal injection of PRL into pseudopregnant rats results in the tyrosine phosphorylation and nuclear translocation of Stat 5. This activated Stat 5 possesses DNA-binding activity for a sequence containing the PRL-inducible element. In addition, luteinization of the PMSG-primed ovary by the administration of hCG is accompanied by an induction of Stat 5 protein.
Ovarian localization
Luteal cells
Comment
Russel et al. (1996) reported that elevated binding of Stat factors to the IL-6RE of the alpha 2M promoter was associated with the expression of alpha 2M mRNA in luteinized granulosa cells and corpora lutea, indicating that activation of Stat factors is one mechanism by which PRL/rPL transactivates the alpha 2M gene in the tissue.
Follicle stages
Corpus luteum
Comment
Phenotypes
Mutations
1 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: subfertile Comment: Among the Stats, the two highly related proteins,Stat5a and Stat5b, are activated by a variety of cytokines. Teglund et al. (1998) the role of the Stat5 proteins by generating mutant mice that have the genes deleted individually or together. The phenotypes of the mice demonstrate an essential, and often redundant, role for the two Stat5 proteins in a spectrum of physiological responses associated with growth hormone and prolactin. Conversely, the responses to a variety of cytokines that activate the Stat5 proteins, including erythropoietin, are largely unaffected.Socolovsky et al show that Stat5 is essential for the high erythropoietic rate during fetal development. Stat5a-/-5b-/- embryos are severely anemic; erythroid progenitors are present in low numbers, show higher levels of apoptosis, and are less responsive to Epo. These findings are
explained by a crucial role for Stat5 in EpoR's antiapoptotic signaling: it mediates the immediate-early induction of Bcl-X(L) in erythroid cells through direct binding to the Bcl-X promoter
These animals have normal developing follicles and ovulation but fewer corpora lutea.