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Title: A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes
Author: Lu, Albert
Tebar Ramon, Francesc
Alvarez-Moya, Blanca
López Alcalá, Cristina
Calvo Ademuz, Maria
Enrich Bastús, Carles
Agell i Jané, Neus
Nakamura, Takeshi
Matsuda, Michiyuki
Bachs Valldeneu, Oriol
Keywords: Proteïnes ras
Transducció de senyal cel·lular
Ras proteins
Cellular signal transduction
Issue Date: 16-Mar-2009
Publisher: Rockefeller University Press
Abstract: Ras proteins are small guanosine triphosphatases involved in the regulation of important cellular functions such as proliferation, differentiation, and apoptosis. Understanding the intracellular trafficking of Ras proteins is crucial to identify novel Ras signaling platforms. In this study, we report that epidermal growth factor triggers Kirsten Ras (KRas) translocation onto endosomal membranes (independently of calmodulin and protein kinase C phosphorylation) through a clathrin-dependent pathway. From early endosomes, KRas but not Harvey Ras or neuroblastoma Ras is sorted and transported to late endosomes (LEs) and lysosomes. Using yellow fluorescent protein¿Raf1 and the Raichu-KRas probe, we identified for the first time in vivo¿active KRas on Rab7 LEs, eliciting a signal output through Raf1. On these LEs, we also identified the p14¿MP1 scaffolding complex and activated extracellular signal-regulated kinase 1/2. Abrogation of lysosomal function leads to a sustained late endosomal mitogen-activated protein kinase signal output. Altogether, this study reveals novel aspects about KRas intracellular trafficking and signaling, shedding new light on the mechanisms controlling Ras regulation in the cell.
Note: Reproducció digital del document publicat a:
It is part of: Journal of Cell Biology, 2009, vol. 184, núm. 6, p. 863-879
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ISSN: 0021-9525
Appears in Collections:Articles publicats en revistes (Biomedicina)

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