title: SOCS3 suppresses the expression of IL-4 cytokine by inhibiting the phosphorylation of c-Jun through the ERK signaling pathway in rat mast cell line RBL-2H3.
abstract: SOCS3 is well known to negatively regulate various cytokine-mediated signaling responses, but its direct role in the expression of specific cytokines has not been clearly elucidated. To understand the role of SOCS3 in the expression of IL-4, one of the key Th2 cytokines, RBL-2H3 cells (a rat mast cell line) were engineered to express SOCS3 constitutively at a high level or at a lower level using shRNA. In RBL-2H3 cells stably expressing SOCS3, the RNA and protein levels of IL-4 were significantly decreased, while it was opposite in RBL-2H3 cells containing shRNA for SOCS3. Overexpression of SOCS3 was found to reduce the level of calcium ionophore-induced phosphorylation of ERK1/2 and c-Jun transcription factor. Consistent with this data, knockdown of SOCS3 increased the level of phosphorylated ERK1 and ERK2. Taken together, SOCS3 appears to play an important role as a negative feedback inhibitor in the expression of IL-4 by inhibiting serine phosphorylation of c-Jun via the ERK signaling pathway.
authors.affiliation: School of Biological Sciences, Seoul National University, Gwanak-gu, Seoul, Republic of Korea.
authors.forename: Donghyun
authors.initials: D
authors.lastname: Kim
authors.forename: Seon-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Sang-Heon
authors.initials: SH
authors.lastname: Cho
authors.forename: Kichul
authors.initials: K
authors.lastname: Shin
authors.forename: Sunyoung
authors.initials: S
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D015847:Interleukin-4 / Q000276:immunology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008407:Mast Cells / Q000276:immunology* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D034741:RNA, Small Interfering; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015847:Interleukin-4; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3