TrkA glycosylation regulates receptor localization and activity

Autor: Watson, F. L., Porcionatto, Marimelia Aparecida [UNIFESP], Bhattacharyya, A., Stiles, C. D., Segal, R. A.
Přispěvatelé: Dana Farber Canc Inst, Harvard Univ, Beth Israel Deaconess Med Ctr, Universidade Federal de São Paulo (UNIFESP)
Jazyk: angličtina
Rok vydání: 1999
Předmět:
Zdroj: Repositório Institucional da UNIFESP
Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
Popis: The human nerve growth factor receptor (TrkA) contains four potential N-glycosylation sites that are highly conserved within the Trk family of neurotrophin receptors, and nine additional sites that are less well conserved. Using a microscale deglycosylation assay, we show here that both conserved and variable N-glycosylation sites are used during maturation of TrkA. Glycosylation at these sites serves two distinct functions, First, glycosylation is necessary to prevent Ligand-independent activation of TrkA, Unglycosylated TrkA core protein is phosphorylated even in the absence of ligand stimulation and displays constitutive kinase activity as well as constitutive interaction with the signaling molecules Shc and PLC-gamma. Second, glycosylation is required to localize TrkA to the cell surface, where it can trigger the Ras/Raf/MAP kinase cascade. Using confocal microscopy, we show that unglycosylated active Trk receptors are trapped intracellularly. Furthermore, the unglycosylated active TrkA receptors are unable to activate kinases in the Ras-MAP kinase pathway, MEK and Erk. Consistent Kith these biochemical observations, unglycosylated TrkA core protein does not promote neuronal differentiation in Trk PC12 cells even at high levels of constitutive catalytic activity, (C) 1999 John Wiley & Sons, Inc. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02115 USA UNIFESP, EPM, Dept Bioquim, Disciplina Biol Mol, São Paulo, Brazil UNIFESP, EPM, Dept Bioquim, Disciplina Biol Mol, São Paulo, Brazil Web of Science
Databáze: OpenAIRE
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