RGD Reference Report - Reelin-mediated signaling locally regulates protein kinase B/Akt and glycogen synthase kinase 3beta. - Rat Genome Database

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Reelin-mediated signaling locally regulates protein kinase B/Akt and glycogen synthase kinase 3beta.

Authors: Beffert, U  Morfini, G  Bock, HH  Reyna, H  Brady, ST  Herz, J 
Citation: Beffert U, etal., J Biol Chem 2002 Dec 20;277(51):49958-64.
RGD ID: 729867
Pubmed: PMID:12376533   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M209205200   (Journal Full-text)

Reelin is a large secreted protein that controls cortical layering by signaling through the very low density lipoprotein receptor and apolipoprotein E receptor 2, thereby inducing tyrosine phosphorylation of the adaptor protein Disabled-1 (Dab1) and suppressing tau phosphorylation in vivo. Here we show that binding of Reelin to these receptors stimulates phosphatidylinositol 3-kinase, resulting in activation of protein kinase B and inhibition of glycogen synthase kinase 3beta. We present genetic evidence that this cascade is dependent on apolipoprotein E receptor 2, very low density lipoprotein receptor, and Dab1. Reelin-signaling components are enriched in axonal growth cones, where tyrosine phosphorylation of Dab1 is increased in response to Reelin. These findings suggest that Reelin-mediated phosphatidylinositol 3-kinase signaling in neuronal growth cones contributes to final neuron positioning in the mammalian brain by local modulation of protein kinase B and glycogen synthase kinase 3beta kinase activities.

Objects referenced in this article
Gene Gsk3b glycogen synthase kinase 3 beta Rattus norvegicus
Gene Reln reelin Rattus norvegicus

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