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

Ding, Heidrun
van Echten-Deckert, Gerhild
Published in European journal of haematology. 2010, vol. 85, no. 2, p. 93-98
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/ metabolismCell MembraneHumansLymphoma, Large-Cell, Anaplastic/ metabolismMembrane Microdomains/chemistry/ physiologyMembrane Proteins/ metabolismPhosphorylationProtein-Tyrosine KinasesSignal Transduction/ physiologySphingolipids/ physiologysrc-Family Kinases/ metabolism
PMID: 20561033
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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

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Deposited on : 2010-08-27

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