Apoptotic cell death influences the signaling activity of the amyloid precursor protein through ShcA and Grb2 adaptor proteins in neuroblastoma SH-SY5Y cells

Journal of Neurochemistry
Valentina VeneziaGennaro Schettini

Abstract

The amyloid precursor protein (APP) is an ubiquitous receptor-like molecule involved in the pathogenesis of Alzheimer's disease (AD). APP and some of its C-terminal proteolytic fragments (CTFs) have been shown to be phosphorylated and to interact with cytosolic phosphotyrosine binding (PTB) domain containing proteins involved in cell signaling and vesicular transport. Among others, the interaction between tyrosine-phosphorylated CTFs and ShcA-Grb2 adaptors is highly enhanced in AD brain. Here we have identified in SH-SY5Y neuroblastoma cells an interaction between APP holoprotein and the adaptor Grb2. Upon activation of apoptotic cell death this interaction is rapidly degraded, APP is partially cleaved and the complex APP/Grb2 is replaced by a new complex between CTFs and ShcA that still involves Grb2. The formation of these complexes is regulated by beta-site APP-cleaving enzyme 1 and influences the phosphorylation of mitogen-activated protein kinase p44/42 extracellular signal-regulated kinase as well as the level of apoptotic death of the cells. These data suggest a dual role in cell signaling for APP and its CTFs in neuroblastoma cells, in a manner similar to that previously reported for other tyrosine kinase receptor, thro...Continue Reading

Citations

Sep 10, 2005·PLoS Genetics·E Camilla ForsbergIrving L Weissman
Feb 6, 2013·PloS One·Andrew F TeichOttavio Arancio
Nov 20, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Susan A AustinColin K Combs
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Apr 5, 2007·Annals of the New York Academy of Sciences·Mario NizzariClaudio Russo
Mar 27, 2007·Annals of the New York Academy of Sciences·Valentina VeneziaClaudio Russo
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Mar 7, 2017·Scientific Reports·Kendra L PuigColin K Combs
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Feb 23, 2007·The Journal of Biological Chemistry·Mario NizzariClaudio Russo
Nov 29, 2020·Metabolism: Clinical and Experimental·Yanjun GuoChengfu Xu

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