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Open Access item Functional Inactivation of CXC Chemokine Receptor 4–mediated Responses through SOCS3 Up-regulation
|Authors:||Soriano, Silvia F.|
Rodríguez Frade, José M.
Martín de Ana, Ana
Carvalho-Pinto, Carla E.
Vila-Coro, Antonio J.
|Keywords:||SOCS3, JAK-STAT activation, Chemokine signaling, Cytokine signaling|
|Publisher:||Rockefeller University Press|
|Citation:||The Journal of Experimental Medicine, Volume 196, Number 3, August 5, 2002, pp. 311–321|
|Abstract:||Hematopoietic cell growth, differentiation, and chemotactic responses require coordinated action between cytokines and chemokines. Cytokines promote receptor oligomerization, followed by Janus kinase
(JAK) kinase activation, signal transducers and transactivators of transcription (STAT) nuclear translocation, and transcription of cytokine-responsive genes. These include
genes that encode a family of negative regulators of cytokine signaling, the suppressors of cytokine signaling (SOCS) proteins. After binding their specific receptors, chemokines trigger receptor
dimerization and activate the JAK/STAT pathway. We show that SOCS3 overexpression
or up-regulation, stimulated by a cytokine such as growth hormone, impairs the response to CXCL12, measured by Ca2+
flux and chemotaxis in vitro and in vivo. This effect is mediated by SOCS3 binding to the CXC chemokine receptor 4 receptor, blocking JAK/STAT and G i
pathways, without interfering with cell surface chemokine receptor expression. The data provide clear evidence for signaling cross-talk between cytokine and chemokine responses in building a functional immune system.|
|Description:||Copyright pertenece a The Rockefeller University Press|
|Appears in Collections:||(CNB) Artículos|
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