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Functional Inactivation of CXC Chemokine Receptor 4–mediated Responses through SOCS3 Up-regulation

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dc.creator Soriano, Silvia F.
dc.creator Hernanz-Falcón, Patricia
dc.creator Rodríguez Frade, José M.
dc.creator Martín de Ana, Ana
dc.creator Garzón, Ruth
dc.creator Carvalho-Pinto, Carla E.
dc.creator Vila-Coro, Antonio J.
dc.creator Zaballos, Ángel
dc.creator Balomenos, Dimitrios
dc.creator Martínez-Alonso, Carlos
dc.creator Mellado, Mario
dc.date 2008-03-24T08:45:11Z
dc.date 2008-03-24T08:45:11Z
dc.date 2002-08
dc.date.accessioned 2017-01-31T01:00:52Z
dc.date.available 2017-01-31T01:00:52Z
dc.identifier The Journal of Experimental Medicine, Volume 196, Number 3, August 5, 2002, pp. 311–321
dc.identifier 0022-1007
dc.identifier http://hdl.handle.net/10261/3276
dc.identifier 10.1084/jem.20012041
dc.identifier.uri http://dspace.mediu.edu.my:8181/xmlui/handle/10261/3276
dc.description Copyright pertenece a The Rockefeller University Press
dc.description 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.
dc.description Peer reviewed
dc.format 385564 bytes
dc.format application/pdf
dc.language eng
dc.publisher Rockefeller University Press
dc.rights openAccess
dc.subject SOCS3
dc.subject JAK-STAT activation
dc.subject Chemokine signaling
dc.subject Cytokine signaling
dc.title Functional Inactivation of CXC Chemokine Receptor 4–mediated Responses through SOCS3 Up-regulation
dc.type Artículo


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