Regulation of multiple cytokine signalling pathways by SOCS3 is independent of SOCS2.
Suppressor of cytokine signalling (SOCS) 3 is an essential regulator of cytokine signalling, and in turn its expression is tightly regulated. Data from overexpression studies in cell lines suggest that SOCS2 regulates SOCS3 protein degradation, by forming a molecular bridge to an E3 ubiquitin-ligase complex. Whether this regulation is relevant in primary cells is unknown. In this study, we utilized Socs2( - / - ) mice to examine the role of SOCS2 in modulating SOCS3 expression and degradation, and its impact on interleukin-2 (IL-2) and IL-6 signalling in primary haemopoietic cells. Both biochemical and biological analyses demonstrated unperturbed SOCS3 expression and cytokine signalling in the absence of SOCS2. Our results suggest that SOCS2 is not a physiological regulator of SOCS3 expression and action in primary haemopoietic cells.
Kiu
Hiu
H
Division of Cancer and Haematology, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, 3050, Australia.
Greenhalgh
Christopher J
CJ
Thaus
Anne
A
Hilton
Douglas J
DJ
Nicola
Nicos A
NA
Alexander
Warren S
WS
Roberts
Andrew W
AW
D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005786:Gene Expression Regulation; D007376:Interleukin-2 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000187:drug effects*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; C491409:Socs2 protein, mouse; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins