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A clathrin-dependent pathway leads to KRas signaling on late endosomes en route to lysosomes
- Source :
- Dipòsit Digital de la UB, Universidad de Barcelona, ResearcherID, Recercat. Dipósit de la Recerca de Catalunya, instname, The Journal of Cell Biology
- Publication Year :
- 2009
- Publisher :
- Rockefeller University Press, 2009.
-
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.
- Subjects :
- Time Factors
Mitogen-Activated Protein Kinase 3
Proteïnes ras
medicine.disease_cause
Anti-apoptotic Ras signalling cascade
Chlorocebus aethiops
Enzyme Inhibitors
Phosphorylation
Research Articles
Protein Kinase C
Mitogen-Activated Protein Kinase 1
Endocytosis
Recombinant Proteins
Cell biology
Protein Transport
COS Cells
Androstenes
Macrolides
KRAS
Signal transduction
Signal Transduction
Cellular signal transduction
Endosome
Recombinant Fusion Proteins
Ras proteins
Endosomes
Biology
Transfection
Clathrin
Article
Calmodulin
medicine
Animals
Humans
Vero Cells
Protein kinase C
GRB2 Adaptor Protein
Epidermal Growth Factor
Cell Membrane
Transducció de senyal cel·lular
Cell Biology
Proto-Oncogene Proteins c-raf
Mutation
ras Proteins
biology.protein
Cancer research
Lysosomes
HeLa Cells
Subjects
Details
- ISSN :
- 15408140 and 00219525
- Volume :
- 184
- Database :
- OpenAIRE
- Journal :
- Journal of Cell Biology
- Accession number :
- edsair.doi.dedup.....6cb365a33e636e509158df04afb798cb