TY - CHAP
T1 - The Negative Regulation of JAK/STAT Signaling
AU - Murphy, James M.
AU - Tannahill, Gillian M.
AU - Hilton, Douglas J.
AU - Greenhalgh, Christopher J.
N1 - Funding Information:
The authors gratefully acknowledge financial support from the National Health and Medical Research Council of Australia (NHMRC; Program Grant 461219) and the National Institutes of Health (Grant ROI-CA-22556). James M. Murphy is the recipient of a CJ Martin (Biomedical) fellowship from the NHMRC; Christopher J. Greenhalgh is the recipient of an NHMRC Industry Fellowship; and Douglas J. Hilton is the recipient of an NHMRC Australia Fellowship.
Publisher Copyright:
© 2010 Elsevier Inc. All rights reserved.
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79960776808&partnerID=8YFLogxK
U2 - 10.1016/B978-0-12-374145-5.00064-4
DO - 10.1016/B978-0-12-374145-5.00064-4
M3 - Chapter (Book)
AN - SCOPUS:79960776808
SP - 467
EP - 480
BT - Handbook of Cell Signaling
A2 - Bradshaw, Ralph A.
A2 - Dennis, Edward A.
PB - Elsevier
CY - Burlington MA USA
ER -