TrkA glycosylation regulates receptor localization and activity

TrkA glycosylation regulates receptor localization and activity

Autor Watson, F. L. Google Scholar
Porcionatto, Marimelia Aparecida Autor UNIFESP Google Scholar
Bhattacharyya, A. Google Scholar
Stiles, C. D. Google Scholar
Segal, R. A. Google Scholar
Instituição Dana Farber Canc Inst
Harvard Univ
Beth Israel Deaconess Med Ctr
Universidade Federal de São Paulo (UNIFESP)
Resumo 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.
Assunto neurotrophins
receptor tyrosine kinases
Idioma Inglês
Data 1999-05-01
Publicado em Journal of Neurobiology. New York: John Wiley & Sons Inc, v. 39, n. 2, p. 323-336, 1999.
ISSN 0022-3034 (Sherpa/Romeo, fator de impacto)
Editor Wiley-Blackwell
Extensão 323-336
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000079811200015

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