The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

Links

 

Gene Review

Stat5b  -  signal transducer and activator of...

Rattus norvegicus

Synonyms: Signal transducer and activator of transcription 5B
 
 
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.
 

Disease relevance of Stat5b

 

High impact information on Stat5b

  • Here we analyze two distinct conserved GH response elements in the rat IGF-I locus that contain paired Stat5b sites [2].
  • Each response element binds Stat5b in vivo in a GH-dependent way, as assessed by chromatin immunoprecipitation assays, and consists of one high affinity and one lower affinity Stat5b site, as determined by both qualitative and quantitative protein-DNA binding studies [2].
  • In contrast, both DNA binding and transactivation domains of Stat5b are required to mediate PRL induction of the beta-casein promoter [3].
  • To understand better the role of Stats in PRL signaling, we cloned rat Stat5b from a PRL-responsive T cell line Nb2 [3].
  • Unexpectedly, activated Stat5 was also detected in the nuclei of untreated control rats. cDNA clones representing Stat3 and two isoforms of Stat5b were isolated from a cDNA library prepared with mRNA from rat livers excised at the peak of an experimental acute phase response [1].
 

Biological context of Stat5b

  • To test the role of Stat5b in GH-stimulated IGF-I gene expression, we have delivered modified versions of the protein to pituitary-deficient male rats by quantitative adenovirus-mediated gene transfer [4].
  • Characterization of distinct Stat5b binding sites that mediate growth hormone-stimulated IGF-I gene transcription [2].
  • Taken together, these results identify an intronic enhancer as a key mediator of GH-induced IGF-I gene transcription working through Stat5b and provide new insight into the molecular architecture of this transcriptional pathway [5].
  • Amino acid sequence analysis identified the 86- and 91-kDa species as two forms of the transcription factor Stat3 and the 92-kDa species as the factor Stat5b [1].
  • In the present study, we found that EGF induced tyrosine phosphorylation of Stat5b both on Tyr-699, which correlated with specific DNA binding activity, and also on other tyrosine residues [6].
 

Anatomical context of Stat5b

  • We previously showed that Stat5b was activated by EGF in rat hepatocytes in primary monolayer culture [6].
  • These effects of AG490 were confirmed in COS cells overexpressing Stat5b [7].
  • Moreover, our findings suggest that progenitor and immature Leydig cells are functional targets for GH in the immature rat, suggestive of a role for GH-Stat5b in testicular development [8].
  • In this report we provide, to our knowledge, the first evidence of Stat5b protein expression in the testis and characterize the activation of Stat5b by these lactogenic hormones in primary rat progenitor, immature and adult Leydig cells, and mouse MA-10 Leydig tumor cells [8].
 

Associations of Stat5b with chemical compounds

 

Enzymatic interactions of Stat5b

 

Regulatory relationships of Stat5b

 

Other interactions of Stat5b

  • The Stat5b response to EGF was most pronounced soon (3 h) after plating (early G(1)) and at high cell density (50,000 hepatocytes per cm(2)) [6].
  • EGF receptor-mediated, c-Src-dependent, activation of Stat5b is downregulated in mitogenically responsive hepatocytes [6].
  • Furthermore, kinase-negative-Jak2, but not AG490, could inhibit Stat5b nuclear translocation and DNA binding [7].
  • Furthermore, we show that Stat5a and Stat5b are continuously phosphorylated in rat prostate in vivo, although they are expressed to varying degree in separate lobes of rat prostate [9].
  • In freshly isolated hepatocytes, EGF activated Stat1, Stat3, and, particularly, Stat5b [10].
 

Analytical, diagnostic and therapeutic context of Stat5b

  • Expression of Stat5b protein and phosphorylated Stat5b protein were investigated by Western blotting using anti-Stat5b pAb and anti-phospho-Stat5a/b pAb [11].
  • The transcription factors signal transducer and activator of transcription (Stat)5a and Stat5b have been implicated in the GH regulation of CYP2C genes in rodent liver [12].

References

  1. Transcription factors Stat3 and Stat5b are present in rat liver nuclei late in an acute phase response and bind interleukin-6 response elements. Ripperger, J.A., Fritz, S., Richter, K., Hocke, G.M., Lottspeich, F., Fey, G.H. J. Biol. Chem. (1995) [Pubmed]
  2. Characterization of distinct Stat5b binding sites that mediate growth hormone-stimulated IGF-I gene transcription. Chia, D.J., Ono, M., Woelfle, J., Schlesinger-Massart, M., Jiang, H., Rotwein, P. J. Biol. Chem. (2006) [Pubmed]
  3. Transcriptional inhibition by Stat5. Differential activities at growth-related versus differentiation-specific promoters. Luo, G., Yu-Lee, L. J. Biol. Chem. (1997) [Pubmed]
  4. Acute control of insulin-like growth factor-I gene transcription by growth hormone through Stat5b. Woelfle, J., Billiard, J., Rotwein, P. J. Biol. Chem. (2003) [Pubmed]
  5. Mechanisms of growth hormone (GH) action. Identification of conserved Stat5 binding sites that mediate GH-induced insulin-like growth factor-I gene activation. Woelfle, J., Chia, D.J., Rotwein, P. J. Biol. Chem. (2003) [Pubmed]
  6. EGF receptor-mediated, c-Src-dependent, activation of Stat5b is downregulated in mitogenically responsive hepatocytes. Guren, T.K., Ødegård, J., Abrahamsen, H., Thoresen, G.H., Susa, M., Andersson, Y., Østby, E., Christoffersen, T. J. Cell. Physiol. (2003) [Pubmed]
  7. PRL-induced ERalpha gene expression is mediated by Janus kinase 2 (Jak2) while signal transducer and activator of transcription 5b (Stat5b) phosphorylation involves Jak2 and a second tyrosine kinase. Frasor, J., Barkai, U., Zhong, L., Fazleabas, A.T., Gibori, G. Mol. Endocrinol. (2001) [Pubmed]
  8. Lactogenic hormone-inducible phosphorylation and gamma-activated site-binding activities of Stat5b in primary rat Leydig cells and MA-10 mouse Leydig tumor cells. Kanzaki, M., Morris, P.L. Endocrinology (1998) [Pubmed]
  9. PRL signal transduction in the epithelial compartment of rat prostate maintained as long-term organ cultures in vitro. Ahonen, T.J., Härkönen, P.L., Rui, H., Nevalainen, M.T. Endocrinology (2002) [Pubmed]
  10. EGF-induced activation of Stat1, Stat3, and Stat5b is unrelated to the stimulation of DNA synthesis in cultured hepatocytes. Guren, T.K., Abrahamsen, H., Thoresen, G.H., Babaie, E., Berg, T., Christoffersen, T. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  11. Effect of erythropoietin on Leydig cell is associated with the activation of Stat5 pathway. Yamazaki, T., Kanzaki, M., Kamidono, S., Fujisawa, M. Mol. Cell. Endocrinol. (2004) [Pubmed]
  12. Possible involvement of truncated signal transducer and activator of transcription-5 in the GH pattern-dependent regulation of CYP2C12 gene expression in rat liver. Helander, H., Gustafsson, J.A., Mode, A. Mol. Endocrinol. (2002) [Pubmed]
 
WikiGenes - Universities