JAK-STAT signaling pathway



The JAK-STAT signaling pathway takes part in the regulation of cellular responses to cytokines and apoptosis. It is particularly important in hematopoiesis - production of blood cells.

Mechanism

  JAKs, which have epidermal growth factor receptor.

The pathway is negatively regulated on multiple levels. Protein tyrosine phosphatases remove phosphates from cytokine receptors as well as activated STATs.[1] More recently identified Suppressors of Cytokine Signaling (SOCS) inhibit STAT phosphorylation by binding and inhibiting JAKs or competing with STATs for phosphotyrosine binding sites on cytokine receptors.[2] STATs are also negatively regulated by Protein Inhibitors of Activated STATs (PIAS), which act in the nucleus through several mechanisms.[3] For example, PIAS1 and PIAS3 inhibit transcriptional activation by STAT1 and STAT3 respectively by binding and blocking access to the DNA sequences they recognise.

References

  1. ^ a b Hebenstreit D, Horejs-Hoeck J and Duschl A (2005) "JAK/STAT-dependent gene regulation by cytokines" in Drug News Perspect Volume 18 (4), pages 243-249. Entrez PubMed 16034480
  2. ^ D. L. Krebs and D. J. Hilton. (2001) "SOCS proteins: negative regulators of cytokine signaling" in Stem Cells Volume 19, pages 378-387. Entrez PubMed 11553846
  3. ^ Shuai K (2006) "Regulation of cytokine signaling pathways by PIAS proteins" Volume 16 (2), pages 196-202. Entrez PubMed 16474434
  • Schroder, K., P. J. Hertzog, T. Ravasi & D. A. Hume (2004) "Interferon-γ: an overview of signals, mechanisms and functions". Journal of Leukocyte Biology 75:163-189.
  • O'Shea, J. J., M. Gadina & R. D. Schreiber (2002) "Cytokine Signaling in 2002: New Surprises in the Jak/Stat Pathway". Cell 109, S121-S131.
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