MOUSE CD24 AS A SIGNALING MOLECULE FOR INTEGRIN-MEDIATED CELL-BINDING- FUNCTIONAL AND PHYSICAL ASSOCIATION WITH SRC-KINASES

CD24 is a differentiation antigen expressed by murine hematopoietic an d neural cells which is linked to the membrane via a glycosylphosphati dylinositol (GPI) anchor. In monocytic ESb-MP cells the molecule serve s as a ligand for P-selectin and triggering with CD24 specific antibod ies can activate VLA-5/L1-mediated cell adhesion in these cells. We re port here that the aggregation is specific for CD24 and not seen with antibodies to the GPI-anchored molecule Thy-1. The Tyr-kinase inhibito r herbimycin can block the aggregation. We studied CD24 associated mol ecules that might be involved in signal transduction. Antibody-mediate d crosslinking of CD24 induced a rapid Tyr-phosphorylation of several cellular proteins in ESb-MP cells which correlated with an elevated ac tivity of p56lck but not p60fyn or MAP-1 kinase. Several phosphorylate d proteins were co-immunoprecipitated with CD24. Re-immunoprecipitatio n allowed the detection of p56lck, p56hck, and p54fyn but not p60fyn, PI-3k, or PLC gamma as a compenent of the CD24 detergent resistant com plex. It is suggested that the CD24-associated kinases are involved in the activation of cell aggregation. (C) 1997 Academic Press.