en
Scientific article
English

The sphingolipid-rich rafts of ALK+ lymphomas downregulate the Lyn-Cbp/PAG signalosome

Published inEuropean journal of haematology, vol. 85, no. 2, p. 93-98
Publication date2010
Abstract

Human anaplastic lymphoma kinase (ALK) + lymphomas express the constitutively active ALK as a fusion protein that drives several survival pathways. The catalytic domain of the anaplastic receptor tyrosine kinase is frequently fused with the nuclear localization protein nucleophosmin but may also fuse with other proteins that associate it with other subcellular structures. Similarly to other B human lymphomas, ALK+ lymphomas express the Cbp/PAG adaptor protein and the non-receptor Lyn kinase in the plasma membrane. In the majority of human lymphomas, the Cbp/PAG adaptor and the Lyn kinase constitute an oncogenic signalosome that serves as a membrane anchor for other signaling enzymes and transcription factors. We show that ALK+ lymphoma membranes harbor sphingolipid-rich microdomains (rafts) in which Lyn is poorly active. However, Lyn activity and consequently Cbp/PAG tyrosine phosphorylation can be restored by extracting sphingolipids from ALK+ lymphoma plasma membranes. In the membrane environment of ALK+ lymphoma rafts, where the glycosphingolipid to signaling protein ratio is higher than in B-NHL rafts, the Lyn activity is suboptimal and does not allow the formation of an efficient Lyn-Cbp/PAG signalosome.

Keywords
  • Adaptor Proteins, Signal Transducing/ metabolism
  • Cell Membrane
  • Humans
  • Lymphoma, Large-Cell, Anaplastic/ metabolism
  • Membrane Microdomains/chemistry/ physiology
  • Membrane Proteins/ metabolism
  • Phosphorylation
  • Protein-Tyrosine Kinases
  • Signal Transduction/ physiology
  • Sphingolipids/ physiology
  • src-Family Kinases/ metabolism
Affiliation Not a UNIGE publication
Citation (ISO format)
YERLY, Stéphane David et al. The sphingolipid-rich rafts of ALK+ lymphomas downregulate the Lyn-Cbp/PAG signalosome. In: European journal of haematology, 2010, vol. 85, n° 2, p. 93–98. doi: 10.1111/j.1600-0609.2010.01492.x
Main files (1)
Article
accessLevelRestricted
Identifiers
ISSN of the journal0902-4441
604views
0downloads

Technical informations

Creation08/27/2010 1:33:34 PM
First validation08/27/2010 1:33:34 PM
Update time03/14/2023 4:02:14 PM
Status update03/14/2023 4:02:14 PM
Last indexation02/12/2024 7:13:13 PM
All rights reserved by Archive ouverte UNIGE and the University of GenevaunigeBlack