title: Complement factor H, vitronectin, and opticin are tyrosine-sulfated proteins of the retinal pigment epithelium.
abstract: Lack of tyrosine sulfation of ocular proteins results in disorganized photoreceptor structure and drastically reduced visual function, demonstrating the importance of this post-translational modification to vision. To understand the role that tyrosine sulfation plays in the function of ocular proteins, we identified some tyrosine-sulfated proteins in the retinal pigment epithelium using two independent methods, immuno-affinity column purification with an anti-sulfotyrosine specific antibody and computer-based sequence analysis of retinal pigment epithelium secretome by means of the prediction program Sulfinator. Radioactive labeling followed by thin layer electrophoresis revealed that three proteins, vitronectin, opticin, and complement factor H (CFH), were post-translationally modified by tyrosine sulfation. The identification of vitronectin and CFH as tyrosine-sulfated proteins is significant, since both are deposited in drusen in the eyes of patients with age-related macular degeneration (AMD). Furthermore, mutations in CFH have been determined to be a major risk factor in the development of AMD. Future studies that seek to understand the role of CFH in the development of AMD should take into account the role that tyrosine sulfation plays in the interaction of this protein with its partners, and examine whether modulating sulfation provides a potential therapeutic target.
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Yogita
authors.initials: Y
authors.lastname: Kanan
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Siefert
authors.affiliation: Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America; Free Radical Biology and Aging Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Kinter
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, United States of America.
authors.forename: Muayyad R
authors.initials: MR
authors.lastname: Al-Ubaidi
mesh_terms: D000368:Aged; D000818:Animals; D017242:Complement Factor H / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D006801:Humans; D008268:Macular Degeneration / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D011499:Protein Processing, Post-Translational / Q000502:physiology; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D019096:Vitronectin / Q000378:metabolism*
chemical_list: D016326:Extracellular Matrix Proteins; D019096:Vitronectin; C005662:tyrosine O-sulfate; D014443:Tyrosine; D017242:Complement Factor H