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Gene Review

STAT5A  -  signal transducer and activator of...

Homo sapiens

Synonyms: MGF, STAT5, Signal transducer and activator of transcription 5A
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Disease relevance of STAT5A

  • Moreover, 4ICD and STAT5A colocalize within nuclei of heregulin beta 1 (HRG)-stimulated cells and both proteins bind to the endogenous beta-casein promoter in T47D breast cancer cells [1].
  • Human immunodeficiency virus type 1 infection inhibits granulocyte-macrophage colony-stimulating factor-induced activation of STAT5A in human monocyte-derived macrophages [2].
  • We conclude that HIV-1 inhibits GM-CSF activation of STAT5A without affecting expression of the known components of the signaling pathway [2].
  • Activation of the Jak2-Stat5 signaling pathway in Nb2 lymphoma cells by an anti-apoptotic agent, aurintricarboxylic acid [3].
  • We review these various defects with an emphasis on the GH-activated JAK2-STAT5 pathway, since this pathway is essential for normal body growth and there has been recent progress in our understanding of the perturbations that occur in uremia [4].
  • We also found that persistently phosphorylated Stat5 in primary cells from patients with myeloid leukemias has a cytoplasmic localization [5].

High impact information on STAT5A


Chemical compound and disease context of STAT5A


Biological context of STAT5A


Anatomical context of STAT5A

  • To determine the functional significance of 4ICD nuclear translocation in a physiologically relevant system, we have demonstrated that cotransfection of ERBB4 and STAT5A in a human breast cancer cell line stimulates beta-casein promoter activity [1].
  • In BCR-Abl transformed K562 cells, STAT5A and 5B are constitutively phosphorylated on tyrosine and are transcriptionally active [17].
  • Granulocyte-macrophage colony-stimulating factor preferentially activates the 94-kD STAT5A and an 80-kD STAT5A isoform in human peripheral blood monocytes [18].
  • Macrophages lost their ability to express the 80-kD STAT5A protein, but retained their ability to activate STAT5A [18].
  • We have reported previously that expression of STAT5B, but not STAT5A, could enhance the transforming potential of v-src and induces cell cycle progression and motility in fibroblasts [19].

Associations of STAT5A with chemical compounds


Physical interactions of STAT5A


Enzymatic interactions of STAT5A

  • MGF-Stat5 can be phosphorylated and activated in its DNA binding activity by Jak2 [27].
  • Ectopically expressed BTK kinase domain was capable of tyrosine-phosphorylating STAT5A both in vitro and in vivo [15].
  • Because Stat5 phosphorylation following cytokine stimulation is generally mediated by Jaks, the lack of Jak activation after TSLP treatment suggested the possibility that tyrosine-phosphorylated Stat5 may be nonfunctional [28].
  • On the other hand, the 92-kDa STAT5 was tyrosine phosphorylated within 1 min of GM-CSF treatment and this was maintained for at least 30 min [29].
  • STAT5 was a major component of this DNA-binding complex, and STAT5 was tyrosine phosphorylated in response to TPO [30].

Regulatory relationships of STAT5A


Other interactions of STAT5A

  • Expression of the dominant-negative form of STAT5B, but not of STAT5A, significantly decreased both p21(waf) expression and the fraction of cells in G1 [34].
  • Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus kinases by interleukins 2 and 15 [35].
  • The present study further analyzed the underlying mechanisms and demonstrated that EPO-mediated STAT5 transactivation in the erythroid AS-E2 cell line was enhanced 6-fold by PGE2 (10 microM), without affecting the STAT5 tyrosine phosphorylation or STAT5-DNA binding [22].
  • Detailed analysis indicated that STAT5A specificity is more similar to that of STAT6 than that of STAT1, as expected from the evolutionary relationships [36].
  • Suppressor of cytokine signaling 7 inhibits prolactin, growth hormone, and leptin signaling by interacting with STAT5 or STAT3 and attenuating their nuclear translocation [37].

Analytical, diagnostic and therapeutic context of STAT5A


  1. The ERBB4/HER4 receptor tyrosine kinase regulates gene expression by functioning as a STAT5A nuclear chaperone. Williams, C.C., Allison, J.G., Vidal, G.A., Burow, M.E., Beckman, B.S., Marrero, L., Jones, F.E. J. Cell Biol. (2004) [Pubmed]
  2. Human immunodeficiency virus type 1 infection inhibits granulocyte-macrophage colony-stimulating factor-induced activation of STAT5A in human monocyte-derived macrophages. Warby, T.J., Crowe, S.M., Jaworowski, A. J. Virol. (2003) [Pubmed]
  3. Activation of the Jak2-Stat5 signaling pathway in Nb2 lymphoma cells by an anti-apoptotic agent, aurintricarboxylic acid. Rui, H., Xu, J., Mehta, S., Fang, H., Williams, J., Dong, F., Grimley, P.M. J. Biol. Chem. (1998) [Pubmed]
  4. Growth hormone resistance in uremia, a role for impaired JAK/STAT signaling. Rabkin, R., Sun, D.F., Chen, Y., Tan, J., Schaefer, F. Pediatr. Nephrol. (2005) [Pubmed]
  5. Constitutive activation of Stat5 promotes its cytoplasmic localization and association with PI3-kinase in myeloid leukemias. Harir, N., Pecquet, C., Kerenyi, M., Sonneck, K., Kovacic, B., Nyga, R., Brevet, M., Dhennin, I., Gouilleux-Gruart, V., Beug, H., Valent, P., Lassoued, K., Moriggl, R., Gouilleux, F. Blood (2007) [Pubmed]
  6. Functional interactions between Stat5 and the glucocorticoid receptor. Stöcklin, E., Wissler, M., Gouilleux, F., Groner, B. Nature (1996) [Pubmed]
  7. Molecular biology of the 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase gene family. Simard, J., Ricketts, M.L., Gingras, S., Soucy, P., Feltus, F.A., Melner, M.H. Endocr. Rev. (2005) [Pubmed]
  8. 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]
  9. Physical and functional interactions between Cas and c-Src induce tamoxifen resistance of breast cancer cells through pathways involving epidermal growth factor receptor and signal transducer and activator of transcription 5b. Riggins, R.B., Thomas, K.S., Ta, H.Q., Wen, J., Davis, R.J., Schuh, N.R., Donelan, S.S., Owen, K.A., Gibson, M.A., Shupnik, M.A., Silva, C.M., Parsons, S.J., Clarke, R., Bouton, A.H. Cancer Res. (2006) [Pubmed]
  10. Convergence of progesterone with growth factor and cytokine signaling in breast cancer. Progesterone receptors regulate signal transducers and activators of transcription expression and activity. Richer, J.K., Lange, C.A., Manning, N.G., Owen, G., Powell, R., Horwitz, K.B. J. Biol. Chem. (1998) [Pubmed]
  11. Naturally occurring dominant-negative Stat5 suppresses transcriptional activity of estrogen receptors and induces apoptosis in T47D breast cancer cells. Yamashita, H., Iwase, H., Toyama, T., Fujii, Y. Oncogene (2003) [Pubmed]
  12. Prognostic significance of signal transducer and activator of transcription 1 activation in breast cancer. Widschwendter, A., Tonko-Geymayer, S., Welte, T., Daxenbichler, G., Marth, C., Doppler, W. Clin. Cancer Res. (2002) [Pubmed]
  13. Hypoxia activates the cyclin D1 promoter via the Jak2/STAT5b pathway in breast cancer cells. Joung, Y.H., Lim, E.J., Lee, M.Y., Park, J.H., Ye, S.K., Park, E.U., Kim, S.Y., Zhang, Z., Lee, K.J., Park, D.K., Park, T., Moon, W.K., Yang, Y.M. Exp. Mol. Med. (2005) [Pubmed]
  14. {beta}1 Integrin and IL-3R coordinately regulate STAT5 activation and anchorage-dependent proliferation. Defilippi, P., Rosso, A., Dentelli, P., Calvi, C., Garbarino, G., Tarone, G., Pegoraro, L., Brizzi, M.F. J. Cell Biol. (2005) [Pubmed]
  15. Transcription factor STAT5A is a substrate of Bruton's tyrosine kinase in B cells. Mahajan, S., Vassilev, A., Sun, N., Ozer, Z., Mao, C., Uckun, F.M. J. Biol. Chem. (2001) [Pubmed]
  16. Constitutive activation of Flt3 and STAT5A enhances self-renewal and alters differentiation of hematopoietic stem cells. Moore, M.A., Dorn, D.C., Schuringa, J.J., Chung, K.Y., Morrone, G. Exp. Hematol. (2007) [Pubmed]
  17. STAT5 activation by BCR-Abl contributes to transformation of K562 leukemia cells. de Groot, R.P., Raaijmakers, J.A., Lammers, J.W., Jove, R., Koenderman, L. Blood (1999) [Pubmed]
  18. 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]
  19. 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]
  20. 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]
  21. Association of CrkL with STAT5 in hematopoietic cells stimulated by granulocyte-macrophage colony-stimulating factor or erythropoietin. Ota, J., Kimura, F., Sato, K., Wakimoto, N., Nakamura, Y., Nagata, N., Suzu, S., Yamada, M., Shimamura, S., Motoyoshi, K. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  22. Prostaglandin-E2 enhances EPO-mediated STAT5 transcriptional activity by serine phosphorylation of CREB. Boer, A.K., Drayer, A.L., Rui, H., Vellenga, E. Blood (2002) [Pubmed]
  23. Tyrosyl phosphorylation and DNA binding activity of signal transducers and activators of transcription (STAT) proteins in hematopoietic cell lines transformed by Bcr/Abl. Carlesso, N., Frank, D.A., Griffin, J.D. J. Exp. Med. (1996) [Pubmed]
  24. Activation of the Jak-Stat- and MAPK-pathways by oncostatin M is not sufficient to cause growth inhibition of human glioma cells. Halfter, H., Postert, C., Friedrich, M., Ringelstein, E.B., Stögbauer, F. Brain Res. Mol. Brain Res. (2000) [Pubmed]
  25. Functional interaction of STAT5 and nuclear receptor co-repressor SMRT: implications in negative regulation of STAT5-dependent transcription. Nakajima, H., Brindle, P.K., Handa, M., Ihle, J.N. EMBO J. (2001) [Pubmed]
  26. Downregulation of JAK3 protein levels in T lymphocytes by prostaglandin E2 and other cyclic adenosine monophosphate-elevating agents: impact on interleukin-2 receptor signaling pathway. Kolenko, V., Rayman, P., Roy, B., Cathcart, M.K., O'Shea, J., Tubbs, R., Rybicki, L., Bukowski, R., Finke, J. Blood (1999) [Pubmed]
  27. Prolactin, growth hormone, erythropoietin and granulocyte-macrophage colony stimulating factor induce MGF-Stat5 DNA binding activity. Gouilleux, F., Pallard, C., Dusanter-Fourt, I., Wakao, H., Haldosen, L.A., Norstedt, G., Levy, D., Groner, B. EMBO J. (1995) [Pubmed]
  28. Requirement for stat5 in thymic stromal lymphopoietin-mediated signal transduction. Isaksen, D.E., Baumann, H., Trobridge, P.A., Farr, A.G., Levin, S.D., Ziegler, S.F. J. Immunol. (1999) [Pubmed]
  29. 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]
  30. Thrombopoietin (TPO) induces tyrosine phosphorylation and activation of STAT5 and STAT3. Bacon, C.M., Tortolani, P.J., Shimosaka, A., Rees, R.C., Longo, D.L., O'Shea, J.J. FEBS Lett. (1995) [Pubmed]
  31. A constitutively active ERBB4/HER4 allele with enhanced transcriptional coactivation and cell-killing activities. Vidal, G.A., Clark, D.E., Marrero, L., Jones, F.E. Oncogene (2007) [Pubmed]
  32. Effects of thrombopoietin, interleukin-3 and the kinase inhibitor K-252a on growth and polyploidization of the megakaryocytic cell line M-07e. Quentmeier, H., Zaborski, M., Drexler, H.G. Leukemia (1998) [Pubmed]
  33. Cytokine-like effects of prolactin in human mononuclear and polymorphonuclear leukocytes. Dogusan, Z., Hooghe, R., Verdood, P., Hooghe-Peters, E.L. J. Neuroimmunol. (2001) [Pubmed]
  34. 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]
  35. Tyrosine phosphorylation and activation of STAT5, STAT3, and Janus kinases by interleukins 2 and 15. Johnston, J.A., Bacon, C.M., Finbloom, D.S., Rees, R.C., Kaplan, D., Shibuya, K., Ortaldo, J.R., Gupta, S., Chen, Y.Q., Giri, J.D. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  36. 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]
  37. Suppressor of cytokine signaling 7 inhibits prolactin, growth hormone, and leptin signaling by interacting with STAT5 or STAT3 and attenuating their nuclear translocation. Martens, N., Uzan, G., Wery, M., Hooghe, R., Hooghe-Peters, E.L., Gertler, A. J. Biol. Chem. (2005) [Pubmed]
  38. A sequence of the CIS gene promoter interacts preferentially with two associated STAT5A dimers: a distinct biochemical difference between STAT5A and STAT5B. Verdier, F., Rabionet, R., Gouilleux, F., Beisenherz-Huss, C., Varlet, P., Muller, O., Mayeux, P., Lacombe, C., Gisselbrecht, S., Chretien, S. Mol. Cell. Biol. (1998) [Pubmed]
  39. TGF-beta does not inhibit IL-12- and IL-2-induced activation of Janus kinases and STATs. Sudarshan, C., Galon, J., Zhou, Y., O'Shea, J.J. J. Immunol. (1999) [Pubmed]
  40. 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]
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