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

Abstract

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.

SOCS3 Protein Developmentally Regulates the Chemokine Receptor CXCR4-FAK Signaling Pathway during B Lymphopoiesis

“…For example, whereas SOCS3 is expressed at low amounts in adult tissues, its expression can be upregulated by growth hormone and a number of cytokines, thus implicating SOCS3 in the negative feedback of cytokine signaling (Alexander, 2002;Johnston and O'Shea, 2003). In this regard, growth hormone-induced SOCS3 expression leads to blockade of JAK and Gi protein association with CXCR4 and impaired chemotaxis (Garzon et al, 2004;Pello et al, 2006;Soriano et al, 2003). In addition, heat shock protein has been reported to regulate CXCR4 signaling in T cells via a similar mechanism (Zanin-Zhorov et al, 2005).…”

Suppressors of cytokine signaling (SOCS) 1 and SOCS3 interact with and modulate fibroblast growth factor receptor signaling

“…As SOCS1 expression can also be enhanced by growth hormone (Fasshauer et al, 2004;Garzon et al, 2004;Larsen and Ropke, 2002), our findings suggest a novel way of cross-talking between cytokine and RTK receptors.…”

SOCS up-regulation mobilizes autologous stem cells through CXCR4 blockade

“…23 Similar effects are induced by SOCS1, which binds JAK to abrogate later signaling events. 55 The higher levels of circulating Sca-1 ϩ c-Kit ϩ Lin Ϫ cells in bGHTg than in wt mice suggested that these effects were due to SOCS-mediated blockade of CXCR4 function. Administration of rhGH to wt mice reproduced the bGHTg mouse phenotype.…”