Recent data suggest that initiation of signal transduction via type 1
Fc epsilon receptor (
Fc epsilon RI) and other immunoreceptors is spatially constrained to
lipid rafts. In order to better understand the complexity and function of these structures, we prepared mAb against
lipid rafts from the rat basophilic
leukemia cell line, RBL-2H3, which is extensively used for analysis of
Fc epsilon RI-mediated activation. One of the
antibodies was found to recognize a novel
glycosylphosphatidylinositol-anchored plasma membrane
glycoprotein of 250
amino acids, designated TEC-21, containing a
cysteine-rich domain homologous to those found in the
urokinase plasminogen activator receptor/Ly-6/snake
neurotoxin family. TEC-21 is abundant on the surface of RBL-2H3 cells (>10 (6) molecules/cell), but is absent in numerous rat tissues except for testes. Aggregation of TEC-21 on RBL-2H3 cells induced a rapid increase in
tyrosine phosphorylation of several substrates including
Syk kinase and LAT adaptor,
calcium flux, and release of secretory components. Similar but more profound activation events were observed in cells activated via
Fc epsilon RI. However, aggregation of TEC-21 did not induce changes in density of
IgE-
Fc epsilon RI complexes,
tyrosine phosphorylation of
Fc epsilon RI beta and gamma subunits, and co-aggregation of Lyn
kinase. TEC-21-induced activation events were also observed in
Fc epsilon RI(-) mutants of RBL-2H3 cells. Thus, TEC-21 is a novel
lipid raft component of RBL-2H3 cells whose aggregation induces activation independently of
Fc epsilon RI.