TrkA glycosylation regulates receptor localization and activity

Autor: Anita Bhattacharyya, Charles D. Stiles, Fiona L. Watson, Marimelia Porcionatto, Rosalind A. Segal
Rok vydání: 1999
Předmět:
Zdroj: Journal of Neurobiology. 39:323-336
ISSN: 1097-4695
0022-3034
DOI: 10.1002/(sici)1097-4695(199905)39:2<323::aid-neu15>3.0.co;2-4
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-γ. 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 with these biochemical observations, unglycosylated TrkA core protein does not promote neuronal differentiation in Trk PC12 cells even at high levels of constitutive catalytic activity. © 1999 John Wiley & Sons, Inc. J Neurobiol 39: 323–336, 1999
Databáze: OpenAIRE
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