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). However,...
This is a preview of subscription content, log in via an institution to check access.
References
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.
Boyer LA, Mathur D, Jaenisch R. Molecular control of pluripotency. Curr Opin Genet Dev. 2006;16(5):455–62.
Bromberg J, Darnell Jr JE. The role of STATs in transcriptional control and their impact on cellular function. Oncogene. 2000;19(21):2468–73.
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.
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.
Hochedlinger K, Jaenisch R. Nuclear reprogramming and pluripotency. Nature. 2006;441(7097):1061–7.
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.
Li WX. Canonical and non-canonical JAK-STAT signaling. Trends Cell Biol. 2008;18(11):545–51.
Lim CP, Cao X. Structure, function, and regulation of STAT proteins. Mol Biosyst. 2006;2(11):536–50.
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.
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.
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.
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.
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.
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.
Silva CM. Role of STATs as downstream signal transducers in Src family kinase-mediated tumorigenesis. Oncogene. 2004;23(48):8017–23.
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.
Yang J, Stark GR. Roles of unphosphorylated STATs in signaling. Cell Res. 2008;18(4):443–51.
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.
Yu H, Jove R. The STATs of cancer–new molecular targets come of age. Nat Rev Cancer. 2004;4(2):97–105.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this entry
Cite this entry
Lim, S.J., Li, W.X. (2012). Phospho- and Unphospho-STATs in Signal Transduction and Gene Regulation (STAT). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-0461-4_636
Download citation
DOI: https://doi.org/10.1007/978-1-4419-0461-4_636
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4419-0460-7
Online ISBN: 978-1-4419-0461-4
eBook Packages: Biomedical and Life SciencesReference Module Biomedical and Life Sciences