Free ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form
MetadataShow full item record
Free ? L chains (F?LCs) are expressed on the surface of myeloma cells and are being assessed as a therapeutic target for the treatment of multiple myeloma. Despite its clinical potential, the mechanism by which F?LCs interact with membranes remains unresolved. In this study, we show that F?LCs associate with sphingomyelin on the plasma membrane of myeloma cells. Moreover, membrane-bound F?LCs are aggregated, suggesting that aggregation is required for intercalation with membranes. Finally, we propose a model where the binding of F?LCs with sphingomyelin on secretory vesicle membranes is stabilized by self-aggregation, with aggregated F?LCs exposed on the plasma membrane after exocytosis. Although it is well known that protein aggregates bind membranes, this is only the second example of an aggregate being found on the surface of cells that also secrete the protein in its native form. We postulate that many other aggregation-prone proteins may associate with cell membranes by similar mechanisms. Copyright© 2010 by The American Association of Immunologists, Inc.
Showing items related by title, author, creator and subject.
Formation of assemblies on cell membranes by secreted proteins: molecular studies of free ? light chain aggregates found on the surface of myeloma cellsHutchinson, A.; Malik, A.; Berkahn, M.; Agostino, Mark; To, J.; Tacchi, J.; Djordjevic, S.; Turnbull, L.; Whitchurch, C.; Edmundson, A.; Jones, D.; Raison, R.; Ramsland, Paul (2013)We have described the presence of cell-membrane-associated ?FLCs (free immunoglobulin light chains) on the surface of myeloma cells. Notably, the anti-?FLC mAb (monoclonal antibody) MDX-1097 is being assessed in clinical ...
Characterization of a unique conformational epitope on free immunoglobulin kappa light chains that is recognized by an antibody with therapeutic potentialHutchinson, A.; Alexova, R.; Bockhorni, V.; Ramsland, Paul; Jones, D.; Jennings, C.; Broady, K.; Edmundson, A.; Raison, R. (2011)The murine mAb, K-1-21, recognizes a conformational epitope expressed on free Ig kappa light chains (FκLCs) and also on cell membrane-associated FκLCs found on kappa myeloma cells. This has led to the development of a ...
Thymoquinone overcomes chemoresistance and enhances the anticancer effects of bortezomib through abrogation of NF-κB regulated gene products in multiple myeloma xenograft mouse modelSiveen, K.; Mustafa, N.; Li, F.; Kannaiyan, R.; Ahn, K.; Kumar, Alan Prem; Chng, W.; Sethi, G. (2014)Multiple myeloma (MM) is a B cell malignancy characterized by clonal proliferation of plasma cells in the bone marrow. With the advent of novel targeted agents, the median survival rate has increased to 5 -7 years. However, ...