FGFR3 intracellular mutations induce tyrosine phosphorylation in the Golgi and defective glycosylation

摘要: Mutations of the Fibroblast Growth Factor Receptor 3 (FGFR3) gene have been implicated in a series skeletal dysplasias including hypochondroplasia, achondroplasia and thanatophoric dysplasia. The severity these diseases ranges from mild dwarfism to severe perinatal lethality, respectively. Although it is considered that mutations give rise constitutively active receptors, remains unclear how different are functionally linked pathologies. By examining various FGFR3 HEK cell culture model, uncharacterized X807R mutation, was found only affecting intracellular domain, induced premature receptor phosphorylation inhibited glycosylation, suggesting tyrosine native inhibits its glycosylation. Moreover, appeared be associated with elevated signaling Golgi apparatus. In conclusion, although pathological could not correlated single factor arising mutations, results suggest domain define distinct means by which mutated disrupt bone development.