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J. Biol. Chem., Vol. 279, Issue 43, 44460-44466, October 22, 2004

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CXCR4-mediated Suppressor of Cytokine Signaling Up-regulation Inactivates Growth Hormone Function^*

Ruth Garzón, Silvia F. Soriano¶, José Miguel Rodríguez-Frade¶, Lucio Gómez¶, Ana Martín de Ana¶, Myriam Sánchez-Gómez, Carlos Martínez-A¶, and Mario Mellado¶||

From the ^¶Department of Immunology and Oncology, Centro Nacional de Biotecnología/Spanish Council for Scientific Research (CSIC), Universidad Autónoma de Madrid, Campus de Cantoblanco, E-28049 Madrid, Spain and the Laboratory of Hormones, Department of Chemistry, Universidad Nacional de Colombia, Bogotá, Colombia

Coordinated action between cytokines and chemokines is required for effective endocrine and immune responses. Proteins of both families promote receptor oligomerization, activation of the Janus kinase (JAK)/STAT pathway, and transcription of many genes, including the suppressor of cytokine signaling (SOCS) family. In this study, we show that chemokine-mediated SOCS1 and SOCS3 up-regulation modulates the signaling and function associated to a cytokine receptor, both in vitro and in vivo. The effect is mediated by SOCS binding to JAK2 and to the cytokine receptor, which blocks subsequent signaling events. The data reinforce the premise of cytokine-chemokine cross-talk, which helps contribute to modulating individual responses and in defining the functional plasticity of the immune system.

Received for publication, July 15, 2004 , and in revised form, August 9, 2004.

^* This work was partially supported by grants from the Spanish Ministerio de Educacion y Ciencia and the European Union. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported by Colciencias, Colombia and by the International Program in Chemical Science of Uppsala University, Sweden.

^|| To whom correspondence should be addressed. Tel.: 34-91-585-4660; Fax: 34-91-372-0493; E-mail: mmellado{at}cnb.uam.es.

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