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2009-03-16

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/25212

A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes

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http://dx.doi.org/10.1083/jcb.200807186

Resum

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.

Matèries

Proteïnes ras, Transducció de senyal cel·lular

Matèries (anglès)

Ras proteins, Cellular signal transduction

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Articles publicats en revistes (Biomedicina)

Citació

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. A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes. _Journal of Cell Biology_. 2009. Vol. 184, núm. 6, pàgs. 863-879. [consulta: 19 de abril de 2026]. ISSN: 0021-9525. [Disponible a: https://hdl.handle.net/2445/25212]

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