Oncostatin M Receptor-β Mutations Underlie Familial Primary Localized Cutaneous Amyloidosis
Autor: | Thais Harumi Sakuma, Hiroshi Shimizu, John A. McGrath, Sian T. Hartshorne, Danilo Nakao Odashiro, Joey Lai-Cheong, Balbir S. Bhogal, Gunter Hans-Filho, Gunter Hans-Neto, Suzanne E. Clements, Ken Arita, Andrew P. South, Maxine V. Holder, Masashi Akiyama, Maçanori Odashiro, Nelise Ritter Hans |
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Rok vydání: | 2008 |
Předmět: |
Keratinocytes
Male DNA Mutational Analysis Molecular Sequence Data Cell Culture Techniques Mutation Missense Sequence Homology Article South Africa Primary cutaneous amyloidosis medicine Genetics Humans Genetics(clinical) Amino Acid Sequence Receptor Genetics (clinical) Genes Dominant Oncostatin M Receptor beta Subunit biology Oncostatin M Oncostatin M receptor medicine.disease United Kingdom Pedigree medicine.anatomical_structure Interleukin-21 receptor Immunology Cancer research biology.protein Chromosomes Human Pair 5 Female Cytokine receptor Keratinocyte Amyloidosis Familial Brazil |
Zdroj: | The American Journal of Human Genetics. 82(1):73-80 |
ISSN: | 0002-9297 |
DOI: | 10.1016/j.ajhg.2007.09.002 |
Popis: | Familial primary localized cutaneous amyloidosis (FPLCA) is an autosomal-dominant disorder associated with chronic skin itching and deposition of epidermal keratin filament-associated amyloid material in the dermis. FPLCA has been mapped to 5p13.1-q11.2, and by candidate gene analysis, we identified missense mutations in the OSMR gene, encoding oncostatin M-specific receptor beta (OSMRbeta), in three families. OSMRbeta is a component of the oncostatin M (OSM) type II receptor and the interleukin (IL)-31 receptor, and cultured FPLCA keratinocytes showed reduced activation of Jak/STAT, MAPK, and PI3K/Akt pathways after OSM or IL-31 cytokine stimulation. The pathogenic amino acid substitutions are located within the extracellular fibronectin type III-like (FNIII) domains, regions critical for receptor dimerization and function. OSM and IL-31 signaling have been implicated in keratinocyte cell proliferation, differentiation, apoptosis, and inflammation, but our OSMR data in individuals with FPLCA represent the first human germline mutations in this cytokine receptor complex and provide new insight into mechanisms of skin itching. |
Databáze: | OpenAIRE |
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