Abstract
The STAT family of transcription factors was first identified in analyses of IFN-mediated signaling pathways (1). Subsequently, several STAT family members were identified, and in vitro studies indicated that individual STAT proteins were phosphorylated on their tyrosine residues in response to distinct cytokines, indicating that the STAT family represents the specificity of cytokines. Indeed, studies with knockout mice clearly established that several STAT family proteins play essential roles in their cytokine-mediated biological functions (2). For instance, Stat1- and Stat2-deficient mice displayed impaired response to IFNs. Stat4 and Stat6 deficiencies resulted in impaired response to IL-12 and IL-4, respectively. Stat5a and Stat5b have been revealed to be important in biological functions mediated by several cytokines, including growth hormone, prolactin, IL-2, and IL-15. All these knockout mice were born normally; however, Stat3 deficiency led to early embryonic lethality. Therefore, in the course of analysis cytokine-mediated function of Stat3 in vivo, a tissue-specific knockout approach was conducted, which revealed the important roles of Stat3 in various tissues in vivo.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Darnell, J. E. Jr., Kerr, I. M., and Stark, G. R. (1994) Science 264, 1415–1421
Takeda, K., and Akira, S. (2000) Cytokine Growth Factor Rev. 11, 199–207
Wegenka, U. M., Buschmann, J., Lutticken, C., Heinrich, P. C., and Horn, F. (1993) Mol Cell Biol 13, 276–288
Akira, S., Nishio, Y., Inoue, M., Wang, X. J., Wei, S., Matsusaka, T., Yoshida, K., Sudo, T., Naruto, M., and Kishimoto, T. (1994) Cell 77, 63–71
Zhong, Z., Wen, Z., and Darnell, J. E. Jr. (1994) Science 264, 95–98
Kishimoto, T., Akira, S., Narazaki, M., and Taga, T. (1995) Blood 86, 1243–1254
Akira, S. (1997) Int J Biochem Cell Biol29, 1401–1418
Takeda, K., Noguchi, K., Shi, W., Tanaka, T., Matsumoto, M., Yoshida, N., Kishimoto, T., and Akira, S. (1997) Proc Natl Acad Sci USA 94, 3 801–3 804
Duncan, S. A., Zhong, Z., Wen, Z., and Darnell, J. E. Jr. (1997). Dev Dyn 208, 190–198
Rajewsky, K., Gu, H., Kuhn, R., Betz, U. A., Muller, W., Roes, J., and Schwenk, F. (1996) J Clin Invest 98, 600–603
Takeda, K., Kaisho T., Yoshida, N., Takeda, J., Kishimoto, T., and Akira, S. (1998) J Immunol 161, 4652–4660
Alonzi, T., Maritano, D., Gorgoni, B., Rizzuto, G., Libert, C., and Poli, V. (2001) Mol Cell Biol21, 1621–1632
Lee, C. K., Raz, R., Gimeno, R., Gertner, R., Wistinghausen, B., Takeshita, K., DePinho, R. A., and Levy, D. E. (2002) Immunity 17, 63–72
Akaishi, H., Takeda, K., Kaisho, T., Shineha, R., Satomi, S., Takeda, J., and Akira, S. (1998) Int Immunol 10, 1747–1751
Takeda, K., Clausen, B., Kaisho, T., Tsujimura, T., Terada, N., Förster, I., and Akira, S. (1999) Immunity 10, 39–49
Kühn, R., Lohler, J., Rennick, D., Rajewsky, K., and Müller, W. (1993) Cell 75, 263–274
Riley, J. K., Takeda, K., Akira, S., and Schreiber, R. D. (1999) J Biol Chem 274, 16513–16521
Kobayashi, M., Kweon, M., Kuwata, H., Kiyono, H., Takeda, K., and Akira, S. (2003) J Clin Invest, 111, 1297–1308
Takeda, K., Kaisho, T., and Akira, S. (2003) Annu Rev Immunol 21, 335–376
Liu, F., Wu, H. Y., Wesselschmidt, R., Kornaga, T. and Link, D. C. (1996) Immunity 5, 491–501
Lieschke, G. J., Grail, D., Hodgson, G., Metcalf, D., Stanley, E., Cheers, C., Fowler, K. J., Basu, S., Zhan, Y. F. and Dunn, A. R. (1994) Blood 84, 1737–1746
McLemore, M. L., Grewal, S., Liu, F., Archambault, A., Poursine-Laurent, J., Haug, J., and Link, D. C. (2001) Immunity 14, 193–204
Sano, S., Itami, S., Takeda, K., Tarutani, M., Yamaguchi, Y., Miura, H., Yoshikawa, K., Akira, S., and Takeda, J. (1999) EMBO J 18, 4657–4668
Sano, S., Takahama, Y., Sugawara, T., Kosaka, H., Itami, S., Yoshikawa, K., Miyazaki, J., van Ewijk, W., and Takeda, J. (2001) Immunity 15, 261–273
Liu, X.W., Robinson, G.W., Wagner, K.U., Garrett, L., WynshawBoris, A., and Hennighausen, L. (1997) Genes Dev 11, 179–186
Liu, X.W., Robinson, G. W., and Hennighausen, L. (1996) Mol Endocrinol 10, 1496–1506
Chapman, R. S., Lourenco, P., Tonner, E., Flint, D. J., Selbert, S., Takeda, K., Akira, S., Clarke, A. R., and Watson, C. J. (1999). Genes Dev 13, 2604–2616
Li, W., Liang, X., Kellendonk, C., Poli, V., and Taub, R. (2002) J Biol Chem 277, 28411–28417
Schweizer, U., Gunnersen, J., Karch, C., Wiese, S, Holtmann B, Takeda K, Akira S, Sendtner M. (2002) J Cell Biol 156, 287–297
Alonzi, T., Middleton, G., Wyatt, S., Buchman, V., Betz, U. A., Müller, W., Musiani, P., Poli, V., and Davies, A. M. (2001) Mol Cell Neurosci 18, 270–282
Hirota, H., Chen, J., Betz, U. A., Rajewsky, K., Gu, Y., Ross, J. Jr., Muller, W., and Chien, K. R. (1999) Cell 97, 189–198
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media Dordrecht
About this chapter
Cite this chapter
Takeda, K., Akira, S. (2003). Tissue-Specific Function of STAT3. In: Sehgal, P.B., Levy, D.E., Hirano, T. (eds) Signal Transducers and Activators of Transcription (STATs). Springer, Dordrecht. https://doi.org/10.1007/978-94-017-3000-6_32
Download citation
DOI: https://doi.org/10.1007/978-94-017-3000-6_32
Publisher Name: Springer, Dordrecht
Print ISBN: 978-90-481-6421-9
Online ISBN: 978-94-017-3000-6
eBook Packages: Springer Book Archive