STAT3 and Transactivation of Steroid Hormone Receptors

Soo ok Lee, Allen C Gao

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Scopus citations

Abstract

The group of transcription factors named signal transducers and activators of transcription (STATs) have been identified as a part of a signaling pathway that initiates in the plasma membrane but quickly translocates to the cytoplasm and to the nucleus to activate transcription of target genes (Bromberg and Darnell, 2000; Darnell, 1997). As its name implies, this family of proteins has the dual function of transducing signals from the cell surface to the nucleus and activating transcription of genes. The STAT signaling initiates binding of ligands, such as cytokines or growth factors, now numbering over 40 types, to receptors in the plasma membrane. This activation of receptors is associated with a cascade of phosphorylations of tyrosine residues on cytoplasmic signaling proteins, which can be caused by the tyrosine kinase activity of the same receptor, through members of the Janus kinase (JAK) family of tyrosine kinases or through nonreceptor tyrosine kinases (e.g., Src and BCR-Abl kinases) that eventually phosphorylate STATs. The phosphorylated STATs then dimerize and translocate to the nucleus, where they bind to specific DNA regulatory elements and activate transcription of target genes. The types of activated STATs vary among cell types, perhaps due to differences in cell surface cytokine or growth factor receptor as well as the JAKs or other nonreceptor tyrosine kinases activated by cytokine or growth factor stimulation. Therefore, depending on the cellular context, the biological response to an extracellular stimulus is a function of the profile of STAT family members that are activated. Many cytokines, hormones, and growth factors use STAT signaling pathways to control a remarkable variety of biological responses, including development, differentiation, cell proliferation, and survival. Given the critical roles of STAT proteins in these fundamental cell processes, it is not surprising that inadequate activation of STAT signaling pathways is also increasingly associated with oncogenesis. Indeed, there is mounting evidence for the involvement of constitutively activated STAT signaling in cell transformation by numerous oncogenes and in malignant progression of many human cancers. STAT proteins have been linked to steroid hormone receptors (SHRs). Particularly, STAT3 has been found to interact with numerous SHRs that participate in the oncogenesis, including androgen receptor (AR), estrogen receptor (ER), and glucocorticoid receptor (GR).

Original languageEnglish (US)
Title of host publicationVitamins and Hormones
Pages333-357
Number of pages25
Volume70
DOIs
StatePublished - 2005
Externally publishedYes

Publication series

NameVitamins and Hormones
Volume70
ISSN (Print)00836729

ASJC Scopus subject areas

  • Endocrinology
  • Biochemistry
  • Physiology

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  • Cite this

    Lee, S. O., & Gao, A. C. (2005). STAT3 and Transactivation of Steroid Hormone Receptors. In Vitamins and Hormones (Vol. 70, pp. 333-357). (Vitamins and Hormones; Vol. 70). https://doi.org/10.1016/S0083-6729(05)70011-X