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Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/3276
Title: Functional Inactivation of CXC Chemokine Receptor 4–mediated Responses through SOCS3 Up-regulation
Authors: Soriano, Silvia F.; Hernanz-Falcón, Patricia; Rodríguez Frade, José M.; Martín de Ana, Ana; Garzón, Ruth; Carvalho-Pinto, Carla E.; Vila-Coro, Antonio J.; Zaballos, Ángel; Balomenos, Dimitrios; Martínez-Alonso, Carlos; Mellado, Mario
Keywords: SOCS3
JAK-STAT activation
Chemokine signaling
Cytokine signaling
Issue Date: Aug-2002
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
URI: http://hdl.handle.net/10261/3276
ISSN: 0022-1007
DOI: 10.1084/jem.20012041
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