title: Prohibitins function as endogenous ligands for Siglec-9 and negatively regulate TCR signaling upon ligation.
abstract: Previously we demonstrated that prohibitin-1 and -2 (prohibitins) were expressed on the surface of T cell leukemia cell lines and activated T lymphocytes. In the present study, we found that prohibitins play a role as counter receptors for Siglec-9 expressed on macrophages and dendritic cells. Siglec-9 bound to prohibitins in a sialic acid-independent manner. Mutated Siglec-9 with Arg(120) changed to Ala lost the binding activity, suggesting a specific ionic peptide-peptide interaction. Phosphorylation of ERK1/2 in Jurkat cells on treatment with anti-CD3 antibody immobilized beads was markedly diminished on treatment with anti-CD3 antibody and Siglec-9 co-immobilized beads, indicating that engagement of prohibitins with Siglec-9 inhibits ERK1/2 phosphorylation. Phosphorylation of c-Raf was also reduced, maybe due to inhibition of the c-Raf-prohibitin interaction by Siglec-9 ligation. In parallel with inhibition of the ERK cascade, IL-2 production was markedly decreased in Jurkat cells. Thus, this interaction may be a useful immunotherapeutic target.
authors.affiliation: Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kamigamo-Motoyama, Kyoto 603-8555, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Yurugi
authors.forename: Shuhei
authors.initials: S
authors.lastname: Tanida
authors.forename: Kaoru
authors.initials: K
authors.lastname: Akita
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishida
authors.forename: Munetoyo
authors.initials: M
authors.lastname: Toda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nakada
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D019169:Jurkat Cells; D008024:Ligands; D008213:Lymphocyte Activation; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D010766:Phosphorylation; D000091402:Prohibitins; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D063265:Sialic Acid Binding Immunoglobulin-like Lectins / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D017252:CD3 Complex; D008024:Ligands; D000091402:Prohibitins; D034741:RNA, Small Interfering; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D012097:Repressor Proteins; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1