title: Novel transmembrane protein 126A (TMEM126A) couples with CD137L reverse signals in myeloid cells.
abstract: Members of the TNF family can promote signals in myeloid cells and both positively and negatively regulate the production of pro-inflammatory cytokines depending on the target myeloid cell type. Using the yeast-two hybrid system, we identified transmembrane protein 126A (TMEM126A) as a binding partner for CD137L (4-1BB ligand). We found that TMEM126A associated and co-localized with CD137L in a mouse macrophage cell line and knockdown of TMEM126A with siRNA abolished the CD137L-induced tyrosine phosphorylation as well as the up-regulation of M-CSF, IL-1β and TN-C expressions. Knockdown of TMEM126A also blocked the down-regulation of IL-1β and IL-6 expressions induced by CD137L in thioglycollate-elicited primary peritoneal macrophages. Knockdown of TMEM126A by stable retroviral TMEM126A shRNA transduction also abolished CD137L-induced tyrosine phosphorylation and cell adherence. These findings identify a novel molecule that bridges TNF family cytokines and pro-inflammatory cytokine secretion in myeloid cells.
authors.affiliation: Institute of Oral Biology, School of Dentistry, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Jun-Sang
authors.initials: JS
authors.lastname: Bae
authors.forename: Joong-Kook
authors.initials: JK
authors.lastname: Choi
authors.forename: Ji-Hoi
authors.initials: JH
authors.lastname: Moon
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
authors.forename: Michael
authors.initials: M
authors.lastname: Croft
authors.forename: Hyeon-Woo
authors.initials: HW
authors.lastname: Lee
mesh_terms: D053330:4-1BB Ligand / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D015536:Down-Regulation; D057809:HEK293 Cells; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016173:Macrophage Colony-Stimulating Factor / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000378:metabolism; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D053330:4-1BB Ligand; D053583:Interleukin-1beta; D015850:Interleukin-6; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C578692:TMEM126A protein, mouse; D016173:Macrophage Colony-Stimulating Factor