The Negative Regulation of JAK/STAT Signaling

James M. Murphy, Gillian M. Tannahill, Douglas J. Hilton, Christopher J. Greenhalgh

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

9 Citations (Scopus)

Abstract

Cytokines are a large family of protein messengers, which are classified into four families based on their structures: hematopoietin, interferon, chemokine, and tumor necrosis factor (TNF). These proteins elicit diverse cellular responses upon binding to cognate transmembrane receptors that are expressed on the surface of target cells. Typically, the intracellular portions of hematopoietin receptors lack any intrinsic kinase activity and are therefore dependent on receptor-associated effectors, such as Janus kinases (JAKs), to initiate signaling pathways. Due to the importance of JAK tyrosine phosphorylation for signal transduction, especially within the activation loop, it follows that dephosphorylation of tyrosine residues is a mechanism employed within the cell to downregulate JAK kinase activity. SHP-1 is a key negative regulator of receptor signaling in hematopoietic and epidermal cells, and has been implicated in dephosphorylating the receptors for EPO, interleukin-3 (IL-3), granulocyte colony-stimulating factor (G-CSF), colony-stimulating factor-1 (CSF-1), Kit ligand/stem cell factor (SCF), and epidermal growth factor (EGF), and the JAK family members, JAK1 and JAK2.

Original languageEnglish
Title of host publicationHandbook of Cell Signaling
EditorsRalph A. Bradshaw, Edward A. Dennis
Place of PublicationBurlington MA USA
PublisherElsevier
Chapter64
Pages467-480
Number of pages14
Edition2nd
ISBN (Electronic)9780123741455
DOIs
Publication statusPublished - 2009
Externally publishedYes

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