CXCR4-mediated suppressor of cytokine signaling up-regulation inactivates growth hormone function.
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.
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.
Ruth
R
Garzón
Silvia F
SF
Soriano
José Miguel
JM
Rodríguez-Frade
Lucio
L
Gómez
Ana
A
Martín de Ana
Myriam
M
Sánchez-Gómez
Carlos
C
Martínez-A
Mario
M
Mellado
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D054377:Chemokine CXCL12; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D053614:Janus Kinase 2; D008024:Ligands; D051379:Mice; D008807:Mice, Inbred BALB C; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry; D012097:Repressor Proteins / Q000378:metabolism; D015398:Signal Transduction; D013154:Spleen / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D015854:Up-Regulation
C515255:CXCL12 protein, human; D002352:Carrier Proteins; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016207:Cytokines; D018972:Insulin-Like Growth Factor Binding Protein 3; D008024:Ligands; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D019718:Receptors, CXCR4; D011994:Recombinant Proteins; D012097:Repressor Proteins; C491590:Socs1 protein, mouse; C491411:Socs3 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014157:Transcription Factors; D012313:RNA; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2