Encyclopedia of Signaling Molecules

2012 Edition
| Editors: Sangdun Choi

Phospho- and Unphospho-STATs in Signal Transduction and Gene Regulation (STAT)

  • Su Jun Lim
  • Willis X. Li
Reference work entry
DOI: https://doi.org/10.1007/978-1-4419-0461-4_636


Historical Background

The STAT (Signal Transducers and Activators of Transcription) proteins were first identified as signaling proteins that function as second messengers and transcription factors in response to cytokines and growth factors (Santos and Costa-Pereira 2011; Li 2008). Mammals have seven STAT genes, namely, STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, and STAT6 (Santos and Costa-Pereira 2011). All the STAT proteins are highly conserved and contain six domains including the SH2, linker, coiled-coil, and DNA binding domain (Bromberg and Darnell 2000). Traditionally, unphosphorylated STAT is believed to reside in the cytoplasm in an inactive form; upon phosphorylation by JAK or another tyrosine kinase, the phosphorylated (active) STAT translocates into the nucleus to induce transcription of target genes (Bromberg and Darnell 2000)....

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  1. Boucheron C, Dumon S, Santos SC, Moriggl R, Hennighausen L, Gisselbrecht S, et al. A single amino acid in the DNA binding regions of STAT5A and STAT5B confers distinct DNA binding specificities. J Biol Chem. 1998;273(51):33936–41.PubMedGoogle Scholar
  2. Boyer LA, Mathur D, Jaenisch R. Molecular control of pluripotency. Curr Opin Genet Dev. 2006;16(5):455–62.PubMedGoogle Scholar
  3. Bromberg J, Darnell Jr JE. The role of STATs in transcriptional control and their impact on cellular function. Oncogene. 2000;19(21):2468–73.PubMedGoogle Scholar
  4. Caldenhoven E, van Dijk TB, Solari R, Armstrong J, Raaijmakers JA, Lammers JW, et al. STAT3beta, a splice variant of transcription factor STAT3, is a dominant negative regulator of transcription. J Biol Chem. 1996;271(22):13221–7.PubMedGoogle Scholar
  5. Dawson MA, Bannister AJ, Gottgens B, Foster SD, Bartke T, Green AR, et al. JAK2 phosphorylates histone H3Y41 and excludes HP1alpha from chromatin. Nature. 2009;461(7265):819–22.PubMedGoogle Scholar
  6. Hochedlinger K, Jaenisch R. Nuclear reprogramming and pluripotency. Nature. 2006;441(7097):1061–7.PubMedGoogle Scholar
  7. Huang H, Li L, Wu C, Schibli D, Colwill K, Ma S, et al. Defining the specificity space of the human SRC homology 2 domain. Mol Cell Proteomics. 2008;7(4):768–84.PubMedGoogle Scholar
  8. Li WX. Canonical and non-canonical JAK-STAT signaling. Trends Cell Biol. 2008;18(11):545–51.PubMedGoogle Scholar
  9. Lim CP, Cao X. Structure, function, and regulation of STAT proteins. Mol Biosyst. 2006;2(11):536–50.PubMedGoogle Scholar
  10. Liu L, McBride KM, Reich NC. STAT3 nuclear import is independent of tyrosine phosphorylation and mediated by importin-alpha3. Proc Natl Acad Sci U S A. 2005;102(23):8150–5.PubMedGoogle Scholar
  11. Marg A, Shan Y, Meyer T, Meissner T, Brandenburg M, Vinkemeier U. Nucleocytoplasmic shuttling by nucleoporins Nup153 and Nup214 and CRM1-dependent nuclear export control the subcellular distribution of latent Stat1. J Cell Biol. 2004;165(6):823–33.PubMedGoogle Scholar
  12. O’Shea JJ, Pesu M, Borie DC, Changelian PS. A new modality for immunosuppression: targeting the JAK/STAT pathway. Nat Rev Drug Discov. 2004;3(7):555–64.PubMedGoogle Scholar
  13. Santos CI, Costa-Pereira AP. Signal transducers and activators of transcription-from cytokine signalling to cancer biology. Biochim Biophys Acta. 2011;1816(1):38–49.PubMedGoogle Scholar
  14. Shi S, Larson K, Guo D, Lim SJ, Dutta P, Yan SJ, et al. Drosophila STAT is required for directly maintaining HP1 localization and heterochromatin stability. Nat Cell Biol. 2008a;10(4):489.PubMedGoogle Scholar
  15. Shi S, Larson K, Guo D, Lim SJ, Dutta P, Yan SJ, et al. Drosophila STAT is required for directly maintaining HP1 localization and heterochromatin stability. Nat Cell Biol. 2008b;10(4):489–96.PubMedGoogle Scholar
  16. Silva CM. Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis. Oncogene. 2004;23(48):8017–23.PubMedGoogle Scholar
  17. Watanabe S, Arai K. Roles of the JAK-STAT system in signal transduction via cytokine receptors. Curr Opin Genet Dev. 1996;6(5):587–96.PubMedGoogle Scholar
  18. Yang J, Stark GR. Roles of unphosphorylated STATs in signaling. Cell Res. 2008;18(4):443–51.PubMedGoogle Scholar
  19. Yang E, Wen Z, Haspel RL, Zhang JJ, Darnell Jr JE. The linker domain of Stat1 is required for gamma interferon-driven transcription. Mol Cell Biol. 1999;19(7):5106–12.PubMedGoogle Scholar
  20. Yu H, Jove R. The STATs of cancer–new molecular targets come of age. Nat Rev Cancer. 2004;4(2):97–105.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.University of Rochester Medical CenterRochesterUSA
  2. 2.Department of MedicineUniversity of California San DiegoLa JollaUSA