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STAT5B  -  signal transducer and activator of...

Homo sapiens

 
 
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Disease relevance of STAT5B

  • A selective decrease in STAT5B was seen 8 days after infection with the BZ167 dual-tropic HIV isolate, but not with the Ba-L, M-tropic strain [1].
  • Our results suggest a role of STAT5B as a regulator of gene expression in diabetes-associated vascular disease [2].
  • In the current study we demonstrate specific activation of STAT5B in epithelial cells representing invasive and metastatic prostate cancer [3].
  • Because we also found preferential constitutive STAT5B activation after transformation of cells by a truncated form of the G-CSF-R that produces severe neutropenia (Kostmann syndrome) and favors leukemia in humans, we discuss the potential role of STAT5B in oncogenic transformation of hematopoietic cells [4].
 

High impact information on STAT5B

  • Expression of the protein tyrosine kinase Lck, a key signaling protein in the TCR complex, activated DNA binding of transfected STAT5A and STAT5B to specific STAT inducible elements [5].
  • We also examined the T cell precursor activity of progenitors expressing dominant-negative forms of PI-3K or STAT5B [6].
  • Diabetic LDL inhibits cell-cycle progression via STAT5B and p21(waf) [2].
  • Whereas 94-kD STAT5A was clearly tyrosine phosphorylated and bound to the enhancer element, the gamma response region (GRR), of the Fc gamma RI gene, substantially less tyrosine phosphorylated STAT5B bound to the immobilized GRR element [7].
  • These results support our hypothesis that specific activation of STAT5, in particular STAT5B, facilitates the progression of prostate cancer [3].
 

Biological context of STAT5B

 

Anatomical context of STAT5B

 

Associations of STAT5B with chemical compounds

  • Substitution of these amino acids demonstrated that a glycine residue at position 433 in STAT5B and a glutamic residue at a similar position in STAT5A determined the DNA binding specificity [15].
 

Physical interactions of STAT5B

  • Functional activation is accompanied by STAT5A but little STAT5B nucleoprotein binding to the IFN-gamma STAT5 site, as determined by competition and supershift assays [16].
 

Regulatory relationships of STAT5B

  • Bandshift experiments showed that in an early stage of both differentiation pathways (14 days), the 94 kDa STAT5B protein was activated by both IL-5 (eosinophil lineage) and GM-CSF (neutrophil lineage) [17].
 

Other interactions of STAT5B

  • There were no specificity differences between STAT5A and STAT5B [18].
  • STAT5A and STAT5B genes belong to the signal transducer and activators of transcription (STAT) family of transcription factors [9].
  • Moreover, STAT5B and STAT3 enhanced gene transcription via separate regulatory elements [10].
  • Activation of STAT5B differed from that of the other two in that the box 3 sequence motif in the cytoplasmic domain of gp130 was not required [10].
  • In co-transfection assays, prolactin-mediated activation but not src kinase-mediated activation of STAT5B resulted in the induction of a beta-casein promoter-driven reporter construct [19].
 

Analytical, diagnostic and therapeutic context of STAT5B

References

  1. HIV-1 infection induces a selective reduction in STAT5 protein expression. Pericle, F., Pinto, L.A., Hicks, S., Kirken, R.A., Sconocchia, G., Rusnak, J., Dolan, M.J., Shearer, G.M., Segal, D.M. J. Immunol. (1998) [Pubmed]
  2. Diabetic LDL inhibits cell-cycle progression via STAT5B and p21(waf). Brizzi, M.F., Dentelli, P., Pavan, M., Rosso, A., Gambino, R., Grazia De Cesaris, M., Garbarino, G., Camussi, G., Pagano, G., Pegoraro, L. J. Clin. Invest. (2002) [Pubmed]
  3. Activation of signal transducer and activator of transcription 5 is required for progression of autochthonous prostate cancer: evidence from the transgenic adenocarcinoma of the mouse prostate system. Kazansky, A.V., Spencer, D.M., Greenberg, N.M. Cancer Res. (2003) [Pubmed]
  4. Differential STAT5 signaling by ligand-dependent and constitutively active cytokine receptors. Moucadel, V., Constantinescu, S.N. J. Biol. Chem. (2005) [Pubmed]
  5. STAT5 interaction with the T cell receptor complex and stimulation of T cell proliferation. Welte, T., Leitenberg, D., Dittel, B.N., al-Ramadi, B.K., Xie, B., Chin, Y.E., Janeway, C.A., Bothwell, A.L., Bottomly, K., Fu, X.Y. Science (1999) [Pubmed]
  6. Distinct roles of the phosphatidylinositol 3-kinase and STAT5 pathways in IL-7-mediated development of human thymocyte precursors. Pallard, C., Stegmann, A.P., van Kleffens, T., Smart, F., Venkitaraman, A., Spits, H. Immunity (1999) [Pubmed]
  7. Granulocyte-macrophage colony-stimulating factor preferentially activates the 94-kD STAT5A and an 80-kD STAT5A isoform in human peripheral blood monocytes. Rosen, R.L., Winestock, K.D., Chen, G., Liu, X., Hennighausen, L., Finbloom, D.S. Blood (1996) [Pubmed]
  8. Characterization and cloning of STAT5 from IM-9 cells and its activation by growth hormone. Silva, C.M., Lu, H., Day, R.N. Mol. Endocrinol. (1996) [Pubmed]
  9. The structure of human STAT5A and B genes reveals two regions of nearly identical sequence and an alternative tissue specific STAT5B promoter. Ambrosio, R., Fimiani, G., Monfregola, J., Sanzari, E., De Felice, N., Salerno, M.C., Pignata, C., D'Urso, M., Ursini, M.V. Gene (2002) [Pubmed]
  10. STAT3 and STAT5B are targets of two different signal pathways activated by hematopoietin receptors and control transcription via separate cytokine response elements. Lai, C.F., Ripperger, J., Morella, K.K., Wang, Y., Gearing, D.P., Horseman, N.D., Campos, S.P., Fey, G.H., Baumann, H. J. Biol. Chem. (1995) [Pubmed]
  11. Mutation of the SHP-2 binding site in growth hormone (GH) receptor prolongs GH-promoted tyrosyl phosphorylation of GH receptor, JAK2, and STAT5B. Stofega, M.R., Herrington, J., Billestrup, N., Carter-Su, C. Mol. Endocrinol. (2000) [Pubmed]
  12. Granulocyte-macrophage colony-stimulating factor-activated signaling pathways in human neutrophils. Selective activation of Jak2, Stat3, and Stat5b. Al-Shami, A., Mahanna, W., Naccache, P.H. J. Biol. Chem. (1998) [Pubmed]
  13. Interleukin-7 induces apoptosis of 697 pre-B cells expressing dominant-negative forms of STAT5: evidence for caspase-dependent and -independent mechanisms. Lanvin, O., Gouilleux, F., Mullié, C., Mazière, C., Fuentes, V., Bissac, E., Dantin, F., Mazière, J.C., Régnier, A., Lassoued, K., Gouilleux-Gruart, V. Oncogene (2004) [Pubmed]
  14. STAT5B-mediated growth hormone signaling is organized by highly dynamic microtubules in hepatic cells. Phung-Koskas, T., Pilon, A., Poüs, C., Betzina, C., Sturm, M., Bourguet-Kondracki, M.L., Durand, G., Drechou, A. J. Biol. Chem. (2005) [Pubmed]
  15. A single amino acid in the DNA binding regions of STAT5A and STAT5B confers distinct DNA binding specificities. Boucheron, C., Dumon, S., Santos, S.C., Moriggl, R., Hennighausen, L., Gisselbrecht, S., Gouilleux, F. J. Biol. Chem. (1998) [Pubmed]
  16. Enhancer role of STAT5 in CD2 activation of IFN-gamma gene expression. Gonsky, R., Deem, R.L., Bream, J., Young, H.A., Targan, S.R. J. Immunol. (2004) [Pubmed]
  17. Differential activation of functionally distinct STAT5 proteins by IL-5 and GM-CSF during eosinophil and neutrophil differentiation from human CD34+ hematopoietic stem cells. Caldenhoven, E., van Dijk, T.B., Tijmensen, A., Raaijmakers, J.A., Lammers, J.W., Koenderman, L., de Groot, R.P. Stem Cells (1998) [Pubmed]
  18. DNA binding specificity of different STAT proteins. Comparison of in vitro specificity with natural target sites. Ehret, G.B., Reichenbach, P., Schindler, U., Horvath, C.M., Fritz, S., Nabholz, M., Bucher, P. J. Biol. Chem. (2001) [Pubmed]
  19. Differential effects of prolactin and src/abl kinases on the nuclear translocation of STAT5B and STAT5A. Kazansky, A.V., Kabotyanski, E.B., Wyszomierski, S.L., Mancini, M.A., Rosen, J.M. J. Biol. Chem. (1999) [Pubmed]
  20. The role of the STAT5 proteins in the proliferation and apoptosis of the CML and AML cells. Baśkiewicz-Masiuk, M., Machaliński, B. Eur. J. Haematol. (2004) [Pubmed]
  21. Polymorphism and chromosomal localization of the porcine signal transducer and activator of transcription 5B gene (STAT5B). Ballester, M., Sardina, M.T., Folch, J.M. J. Anim. Breed. Genet. (2006) [Pubmed]
 
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