Abstract
Signal Transducers and Activators of Transcription (STATs) are key components of the JAK/STAT pathway. Of the seven STATs, STAT5A and STAT5B are of particular interest for their critical roles in cellular differentiation, adipogenesis, oncogenesis, and immune function. The interactions of STAT5A and STAT5B with cytokine/hormone receptors, nuclear receptors, transcriptional regulators, proto-oncogenes, kinases, and phosphatases all contribute to modulating STAT5 activity. Among these STAT5 interacting proteins, some serve as coactivators or corepressors to regulate STAT5 transcriptional activity and some proteins can interact with STAT5 to enhance or repress STAT5 signaling. In addition, a few STAT5 interacting proteins have been identified as positive regulators of STAT5 that alter serine and tyrosine phosphorylation of STAT5 while other proteins have been identified as negative regulators of STAT5 via dephosphorylation. This review article will discuss how STAT5 activity is modulated by proteins that physically interact with STAT5.
Highlights
Both STAT5A and STAT5B are activated by phosphorylation at Tyr694 and Tyr699, respectively, by JAK2, which is activated by the binding of numerous cytokines and hormones including growth hormone (GH), erythropoietin (EPO), prolactin (PRL), and several interleukins (ILs) to their receptors [13]
In IL-2 stimulated CTLL-20 cells, the cytosolic Protein tyrosine phosphatases (PTPs), SHP-2 (SH2 domain containing protein tyrosine phosphatase), was shown to dephosphorylate STAT5A on tyrosine694 and STAT5B on tyrosine699 [75]. This modification occurred in the cytosol and was not dependent on signal transducers and activators of transcription (STATs) nuclear translocation. These results suggest that SHP-2 functions to negatively regulate STAT5 activity [75]
The discovery of STATs over twenty-five years ago revealed a new intracellular signaling pathway that mediated the actions of dozens of different growth factors, hormones, and cytokines
Summary
The JAK-STAT signaling pathway transmits extracellular signals to the nucleus and regulates a variety of cellular activities including apoptosis, differentiation, proliferation, and immunological responses. This pathway consists of receptor-associated Janus kinases (JAKs), signal transducers and activators of transcription (STATs), and a cytokine or hormone receptor [1]. The JAKs are a family of tyrosine kinases that are activated by the binding of ligands that includes growth factors, hormones, interferons, and a variety of cytokines to their specific receptors. Active STATs form a dimer and translocate to the nucleus where they. UponTransducers phosphorylation, active STATs form a dimer and translocate to the nucleus where they modulate transcription
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