title: Murine insulin growth factor-like (IGFL) and human IGFL1 proteins are induced in inflammatory skin conditions and bind to a novel tumor necrosis factor receptor family member, IGFLR1.
abstract: Psoriasis is a human skin condition characterized by epidermal hyperproliferation and infiltration of multiple leukocyte populations. In characterizing a novel insulin growth factor (IGF)-like (IGFL) gene in mice (mIGFL), we found transcripts of this gene to be most highly expressed in skin with enhanced expression in models of skin wounding and psoriatic-like inflammation. A possible functional ortholog in humans, IGFL1, was uniquely and significantly induced in psoriatic skin samples. In vitro IGFL1 expression was up-regulated in cultured primary keratinocytes stimulated with tumor necrosis factor α but not by other psoriasis-associated cytokines. Finally, using a secreted and transmembrane protein library, we discovered high affinity interactions between human IGFL1 and mIGFL and the TMEM149 ectodomain. TMEM149 (renamed here as IGFLR1) is an uncharacterized gene with structural similarity to the tumor necrosis factor receptor family. Our studies demonstrate that IGFLR1 is expressed primarily on the surface of mouse T cells. The connection between mIGFL and IGFLR1 receptor suggests mIGFL may influence T cell biology within inflammatory skin conditions.
authors: Department of Protein Chemistry, Genentech, Inc, South San Francisco, California 94080-4918, USA.
authors: Adrian A
authors: AA
authors: Lobito
authors: Sree R
authors: SR
authors: Ramani
authors: Irene
authors: I
authors: Tom
authors: J Fernando
authors: JF
authors: Bazan
authors: Elizabeth
authors: E
authors: Luis
authors: Wayne J
authors: WJ
authors: Fairbrother
authors: Wenjun
authors: W
authors: Ouyang
authors: Lino C
authors: LC
authors: Gonzalez
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D017434:Protein Structure, Tertiary; D011565:Psoriasis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D014947:Wounds and Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D007334:Insulin-Like Growth Factor I