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)



Gene Review

Stat5a  -  signal transducer and activator of...

Mus musculus

Synonyms: AA959963, Mammary gland factor, Mgf, Mpf, STAT5, ...
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 Stat5a


Psychiatry related information on Stat5a

  • Mammary-directed expression of the wild-type Stat5, constitutively activated Stat5 and carboxyl-terminally truncated dominant negative Stat5 forms resulted in mammary tumors with incidence rates of up to 22% and latency periods of 8-12 months [5].

High impact information on Stat5a

  • Fetal anemia and apoptosis of red cell progenitors in Stat5a-/-5b-/- mice: a direct role for Stat5 in Bcl-X(L) induction [6].
  • Stat5 is rapidly activated following EpoR stimulation, but its function in erythropoiesis has been unclear since adult Stat5a-/-5b-/- mice have normal steady-state hematocrit [6].
  • Here we show that Stat5 is essential for the high erythropoietic rate during fetal development [6].
  • Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses [7].
  • 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 [7].

Chemical compound and disease context of Stat5a


Biological context of Stat5a


Anatomical context of Stat5a


Associations of Stat5a with chemical compounds

  • Although activated by IL-7, Stat5a/b (Stat, signal transducer and activator of transcription) have been thought to play limited roles in lymphoid development [18].
  • In C2C12 myotubes, we find that insulin stimulates tyrosine phosphorylation of Stat5a and Stat5b by 3-5-fold [19].
  • Here, we show that injection of glucose or insulin into fasted mice leads to robust activation of both Stat5a and Stat5b in skeletal muscle [19].
  • In female mice, however, disruption of either Stat5a or Stat5b led to striking decreases in several liver CYP-catalyzed testosterone hydroxylase activities [20].
  • These results define a negative cross talk between PR and Stat5a/GR that may contribute to the physiological role of progesterone to repress lactogenic hormone induction of the beta-casein gene in the mammary gland during pregnancy [21].
  • GH effectively protected Stat5(+/+) cells against glutamate toxicity but had no effect in Stat5(-/-) neurons or in Stat5(+/+) neurons treated with JAK2/Stat or PI3K inhibitor [22].

Physical interactions of Stat5a

  • IL-2 induced the binding of Stat5a and b proteins to the human GASd element [23].
  • Furthermore, chromatin immunoprecipitation assays revealed that Stat5a binds to the SOCS3 promoter in CD4(+) T cells [24].
  • In transient transfection experiments, Socs1 physically interacts with TEL-Jak2 and interferes with the TEL-Jak2-induced phosphorylation and activation of Stat5 factors, probably through the Socs1-induced proteasome-mediated degradation of the fusion protein [25].
  • EMSA analysis using a Stat 5 binding site showed both PRLs to cause equivalent binding of nuclear proteins and that most of what bound was complexed through Stat 5a [26].
  • However, following prolactin induction the Ser(725) mutant displayed sustained DNA binding activity compared with that of wild type Stat5a [27].

Enzymatic interactions of Stat5a

  • In turn, JAK2 phosphorylates and activates STAT5, a member of the signal transducers and activators of transcription (STAT) family [28].
  • In addition, Lyn was demonstrated to phosphorylate the EpoR and Stat5 on tyrosines in vitro [29].
  • We have previously shown that in HC11 mammary epithelial cells Stat5a is phosphorylated on Tyr(694) in a prolactin-sensitive manner, whereas serine phosphorylation is constitutive (Wartmann, M., Cella, N., Hofer, P., Groner, B., Xiuwen, L., Hennighausen, L., and Hynes, N. E. (1996) J. Biol. Chem. 271, 31863-31868) [27].
  • A common epitope is shared by activated signal transducer and activator of transcription-5 (STAT5) and the phosphorylated erythropoietin receptor: implications for the docking model of STAT activation [30].
  • Our results suggest that STAT5 phosphorylated by IL-7 can directly up-regulate Pax5 transcription in early B cells [31].

Regulatory relationships of Stat5a


Other interactions of Stat5a

  • Correspondingly, we show that Stat5a is essential for maximal responsiveness to antigenic stimuli in vivo, underscoring the physiological importance of IL-2-induced IL-2R alpha expression [15].
  • The increase of Stat5 expression during pregnancy coincides with the activation of the WAP gene [36].
  • A comparative analysis of Jak2-deficient mammary glands with transplants from Stat5a/b knockouts revealed that Jak2 deficiency also impairs the pregnancy-induced branching morphogenesis [37].
  • Pre- and pro-B cells of Stat5-deficient animals were found to have reduced responses to IL-7 [38].
  • However, it is the relative importance and redundancy of Stat6 and Stat5a in Th2 cell differentiation and allergic airway inflammation are unknown [39].
  • In vitro kinase assays revealed that STAT5 is a direct target of Flt3 [40].

Analytical, diagnostic and therapeutic context of Stat5a


  1. Stat5 synergizes with T cell receptor/antigen stimulation in the development of lymphoblastic lymphoma. Kelly, J.A., Spolski, R., Kovanen, P.E., Suzuki, T., Bollenbacher, J., Pise-Masison, C.A., Radonovich, M.F., Lee, S., Jenkins, N.A., Copeland, N.G., Morse, H.C., Leonard, W.J. J. Exp. Med. (2003) [Pubmed]
  2. Constitutive activation of Stat5b contributes to carcinogenesis in vivo. Xi, S., Zhang, Q., Gooding, W.E., Smithgall, T.E., Grandis, J.R. Cancer Res. (2003) [Pubmed]
  3. Loss of Stat5a delays mammary cancer progression in a mouse model. Ren, S., Cai, H.R., Li, M., Furth, P.A. Oncogene (2002) [Pubmed]
  4. Epithelial defect in prostates of Stat5a-null mice. Nevalainen, M.T., Ahonen, T.J., Yamashita, H., Chandrashekar, V., Bartke, A., Grimley, P.M., Robinson, G.W., Hennighausen, L., Rui, H. Lab. Invest. (2000) [Pubmed]
  5. Deregulation of Stat5 expression and activation causes mammary tumors in transgenic mice. Iavnilovitch, E., Cardiff, R.D., Groner, B., Barash, I. Int. J. Cancer (2004) [Pubmed]
  6. Fetal anemia and apoptosis of red cell progenitors in Stat5a-/-5b-/- mice: a direct role for Stat5 in Bcl-X(L) induction. Socolovsky, M., Fallon, A.E., Wang, S., Brugnara, C., Lodish, H.F. Cell (1999) [Pubmed]
  7. Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Teglund, S., McKay, C., Schuetz, E., van Deursen, J.M., Stravopodis, D., Wang, D., Brown, M., Bodner, S., Grosveld, G., Ihle, J.N. Cell (1998) [Pubmed]
  8. Stat5a is tyrosine phosphorylated and nuclear localized in a high proportion of human breast cancers. Cotarla, I., Ren, S., Zhang, Y., Gehan, E., Singh, B., Furth, P.A. Int. J. Cancer (2004) [Pubmed]
  9. Activation of the JAK1-STAT5 pathway by binding of the Friend virus gp55 glycoprotein to the erythropoietin receptor. Yamamura, Y., Senda, H., Noda, M., Ikawa, Y. Leukemia (1997) [Pubmed]
  10. Stat5a is mandatory for adult mammary gland development and lactogenesis. Liu, X., Robinson, G.W., Wagner, K.U., Garrett, L., Wynshaw-Boris, A., Hennighausen, L. Genes Dev. (1997) [Pubmed]
  11. Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells. Moriggl, R., Topham, D.J., Teglund, S., Sexl, V., McKay, C., Wang, D., Hoffmeyer, A., van Deursen, J., Sangster, M.Y., Bunting, K.D., Grosveld, G.C., Ihle, J.N. Immunity (1999) [Pubmed]
  12. Essential functions of p21-activated kinase 1 in morphogenesis and differentiation of mammary glands. Wang, R.A., Vadlamudi, R.K., Bagheri-Yarmand, R., Beuvink, I., Hynes, N.E., Kumar, R. J. Cell Biol. (2003) [Pubmed]
  13. Clarifying the role of Stat5 in lymphoid development and Abelson-induced transformation. Hoelbl, A., Kovacic, B., Kerenyi, M.A., Simma, O., Warsch, W., Cui, Y., Beug, H., Hennighausen, L., Moriggl, R., Sexl, V. Blood (2006) [Pubmed]
  14. Antiapoptotic activity of Stat5 required during terminal stages of myeloid differentiation. Kieslinger, M., Woldman, I., Moriggl, R., Hofmann, J., Marine, J.C., Ihle, J.N., Beug, H., Decker, T. Genes Dev. (2000) [Pubmed]
  15. An indirect effect of Stat5a in IL-2-induced proliferation: a critical role for Stat5a in IL-2-mediated IL-2 receptor alpha chain induction. Nakajima, H., Liu, X.W., Wynshaw-Boris, A., Rosenthal, L.A., Imada, K., Finbloom, D.S., Hennighausen, L., Leonard, W.J. Immunity (1997) [Pubmed]
  16. Stat5 is essential for the myelo- and lymphoproliferative disease induced by TEL/JAK2. Schwaller, J., Parganas, E., Wang, D., Cain, D., Aster, J.C., Williams, I.R., Lee, C.K., Gerthner, R., Kitamura, T., Frantsve, J., Anastasiadou, E., Loh, M.L., Levy, D.E., Ihle, J.N., Gilliland, D.G. Mol. Cell (2000) [Pubmed]
  17. Stat5a regulates T helper cell differentiation by several distinct mechanisms. Kagami , S., Nakajima, H., Suto, A., Hirose, K., Suzuki, K., Morita, S., Kato, I., Saito, Y., Kitamura, T., Iwamoto, I. Blood (2001) [Pubmed]
  18. Stat5a/b are essential for normal lymphoid development and differentiation. Yao, Z., Cui, Y., Watford, W.T., Bream, J.H., Yamaoka, K., Hissong, B.D., Li, D., Durum, S.K., Jiang, Q., Bhandoola, A., Hennighausen, L., O'Shea, J.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  19. Insulin Induction of SOCS-2 and SOCS-3 mRNA expression in C2C12 Skeletal Muscle Cells Is Mediated by Stat5*. Sadowski, C.L., Choi, T.S., Le, M., Wheeler, T.T., Wang, L.H., Sadowski, H.B. J. Biol. Chem. (2001) [Pubmed]
  20. Distinctive roles of STAT5a and STAT5b in sexual dimorphism of hepatic P450 gene expression. Impact of STAT5a gene disruption. Park, S.H., Liu, X., Hennighausen, L., Davey, H.W., Waxman, D.J. J. Biol. Chem. (1999) [Pubmed]
  21. Progesterone Receptor Repression of Prolactin/Signal Transducer and Activator of Transcription 5-Mediated Transcription of the {beta}-Casein Gene in Mammary Epithelial Cells. Buser, A.C., Gass-Handel, E.K., Wyszomierski, S.L., Doppler, W., Leonhardt, S.A., Schaack, J., Rosen, J.M., Watkin, H., Anderson, S.M., Edwards, D.P. Mol. Endocrinol. (2007) [Pubmed]
  22. Essential role for Stat5 in the neurotrophic but not in the neuroprotective effect of erythropoietin. Byts, N., Samoylenko, A., Fasshauer, T., Ivanisevic, M., Hennighausen, L., Ehrenreich, H., Sirén, A.L. Cell Death Differ. (2008) [Pubmed]
  23. Elf-1 and Stat5 bind to a critical element in a new enhancer of the human interleukin-2 receptor alpha gene. Lécine, P., Algarté, M., Rameil, P., Beadling, C., Bucher, P., Nabholz, M., Imbert, J. Mol. Cell. Biol. (1996) [Pubmed]
  24. Stat5a inhibits IL-12-induced Th1 cell differentiation through the induction of suppressor of cytokine signaling 3 expression. Takatori, H., Nakajima, H., Kagami, S., Hirose, K., Suto, A., Suzuki, K., Kubo, M., Yoshimura, A., Saito, Y., Iwamoto, I. J. Immunol. (2005) [Pubmed]
  25. The TEL-Jak2 oncoprotein induces Socs1 expression and altered cytokine response in Ba/F3 cells. Monni, R., Santos, S.C., Mauchauffe, M., Berger, R., Ghysdael, J., Gouilleux, F., Gisselbrecht, S., Bernard, O., Penard-Lacronique, V. Oncogene (2001) [Pubmed]
  26. Different biological effects of unmodified prolactin and a molecular mimic of phosphorylated prolactin involve different signaling pathways. Wu, W., Coss, D., Lorenson, M.Y., Kuo, C.B., Xu, X., Walker, A.M. Biochemistry (2003) [Pubmed]
  27. Stat5a serine phosphorylation. Serine 779 is constitutively phosphorylated in the mammary gland, and serine 725 phosphorylation influences prolactin-stimulated in vitro DNA binding activity. Beuvink, I., Hess, D., Flotow, H., Hofsteenge, J., Groner, B., Hynes, N.E. J. Biol. Chem. (2000) [Pubmed]
  28. A cytosolic protein-tyrosine phosphatase PTP1B specifically dephosphorylates and deactivates prolactin-activated STAT5a and STAT5b. Aoki, N., Matsuda, T. J. Biol. Chem. (2000) [Pubmed]
  29. Lyn physically associates with the erythropoietin receptor and may play a role in activation of the Stat5 pathway. Chin, H., Arai, A., Wakao, H., Kamiyama, R., Miyasaka, N., Miura, O. Blood (1998) [Pubmed]
  30. A common epitope is shared by activated signal transducer and activator of transcription-5 (STAT5) and the phosphorylated erythropoietin receptor: implications for the docking model of STAT activation. Barber, D.L., Beattie, B.K., Mason, J.M., Nguyen, M.H., Yoakim, M., Neel, B.G., D'Andrea, A.D., Frank, D.A. Blood (2001) [Pubmed]
  31. EBF-regulating Pax5 transcription is enhanced by STAT5 in the early stage of B cells. Hirokawa, S., Sato, H., Kato, I., Kudo, A. Eur. J. Immunol. (2003) [Pubmed]
  32. Erythropoietin induces sustained phosphorylation of STAT5 in primitive but not definitive erythrocytes generated from mouse embryonic stem cells. Tsuji-Takayama, K., Otani, T., Inoue, T., Nakamura, S., Motoda, R., Kibata, M., Orita, K. Exp. Hematol. (2006) [Pubmed]
  33. Interleukin-3 signals through multiple isoforms of Stat5. Azam, M., Erdjument-Bromage, H., Kreider, B.L., Xia, M., Quelle, F., Basu, R., Saris, C., Tempst, P., Ihle, J.N., Schindler, C. EMBO J. (1995) [Pubmed]
  34. STAT5A-deficient mice demonstrate a defect in granulocyte-macrophage colony-stimulating factor-induced proliferation and gene expression. Feldman, G.M., Rosenthal, L.A., Liu, X., Hayes, M.P., Wynshaw-Boris, A., Leonard, W.J., Hennighausen, L., Finbloom, D.S. Blood (1997) [Pubmed]
  35. Nuclear factor I and mammary gland factor (STAT5) play a critical role in regulating rat whey acidic protein gene expression in transgenic mice. Li, S., Rosen, J.M. Mol. Cell. Biol. (1995) [Pubmed]
  36. Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in prolactin signal transduction in mouse mammary tissue. Liu, X., Robinson, G.W., Gouilleux, F., Groner, B., Hennighausen, L. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  37. Impaired alveologenesis and maintenance of secretory mammary epithelial cells in Jak2 conditional knockout mice. Wagner, K.U., Krempler, A., Triplett, A.A., Qi, Y., George, N.M., Zhu, J., Rui, H. Mol. Cell. Biol. (2004) [Pubmed]
  38. Stat5a/b contribute to interleukin 7-induced B-cell precursor expansion, but abl- and bcr/abl-induced transformation are independent of stat5. Sexl, V., Piekorz, R., Moriggl, R., Rohrer, J., Brown, M.P., Bunting, K.D., Rothammer, K., Roussel, M.F., Ihle, J.N. Blood (2000) [Pubmed]
  39. Indispensable role of Stat5a in Stat6-independent Th2 cell differentiation and allergic airway inflammation. Takatori, H., Nakajima, H., Hirose, K., Kagami, S., Tamachi, T., Suto, A., Suzuki, K., Saito, Y., Iwamoto, I. J. Immunol. (2005) [Pubmed]
  40. Activation mechanisms of STAT5 by oncogenic Flt3-ITD. Choudhary, C., Brandts, C., Schwable, J., Tickenbrock, L., Sargin, B., Ueker, A., Böhmer, F.D., Berdel, W.E., Müller-Tidow, C., Serve, H. Blood (2007) [Pubmed]
  41. Characterization of Stat5a and Stat5b homodimers and heterodimers and their association with the glucocortiocoid receptor in mammary cells. Cella, N., Groner, B., Hynes, N.E. Mol. Cell. Biol. (1998) [Pubmed]
  42. Constitutively active signal transducer and activator of transcription 5 can replace the requirement for growth hormone in adipogenesis of 3T3-F442A preadipocytes. Shang, C.A., Waters, M.J. Mol. Endocrinol. (2003) [Pubmed]
WikiGenes - Universities