SNSF | P3 Research Database

Transmembrane interactions in lymphocytes: Sphingolipid micro- domains in lymphocyte signaling

English title	Transmembrane interactions in lymphocytes: Sphingolipid micro- domains in lymphocyte signaling
Applicant	Hoessli Daniel
Number	102158
Funding scheme	Project funding
Research institution	Département de Pathologie et Immunologie Faculté de Médecine / CMU Université de Genève
Institution of higher education	University of Geneva - GE
Main discipline	Cellular Biology, Cytology
Start/End	01.10.2003 - 30.09.2006
Approved amount	202'938.00

Lead

Lay summary
In all B lymphoma cell lines tested, Lyn and Cbp/PAG appear to be associated and selectively concentrated in sphingolipid-rich, raft microdomains, wherein the Lyn activity is optimal. The Lyn-Cbp/PAG interaction thus relies on protein-protein contacts and its catalytic function is dependent on the sphingolipid environment of the raft microdomains. This activity does not require cross-linking of surface components, unlike what is needed to signal through rafts (crosslinking of GPI-linked surface proteins, for instance). The lymphoma signalling machinery is therefore constitutively activated (constitutively activated signalosome). With the exception of Burkitt-derived Raji cells that are resistant to cell death, despite inhibition of Lyn in rafts, all other B-lymphoma cell lines undergo cell death following Lyn inhibition.Moreover, in selected cell lines, we have shown that Lyn inhibition can also result from altering the raft membrane. Several B-lymphoma cell lines are therefore vulnerable at the Lyn kinase, as well as in their raft microdomain organization. We think that our results open up new and realistic therapeutic possibilities.

Last update: 21.02.2013