Compartmentalization of B-cell antigen receptor functions

Receptor tyrosine kinases (RTK), like the PDGF-receptor, translate information from the extracellular environment into cytoplasmic signals that regulate a spectrum of cellular functions. RTK molecules consist of ligand binding extracellular domains, cytoplasmic kinase domains and tyrosine phosphorylation sites [Ullrich and Schlessinger, 1990 (Cell 61, 203-212); Heldin, 1992 (EMBO J. 11, 4251-4259)]. Upon ligand-induced RTK oligomerization, the kinase domains will become activated and induce auto(trans)phosphorylation of a number of cytoplasmic tyrosine residues. These phosphorylated tyrosine residues are incorporated in distinct sequence motifs and act as specific docking sites for SH2 domain-containing proteins [Songyang et al., 1993 (Cell 72, 767-778)]. In contrast to single- or oligo-chain RTK, immunological receptors such as antigen receptors, FcR and cytokine receptors are multi-chain complexes in which distinct receptor functions appear to be compartmentalized in distinct polypeptides. Here, we summarize current knowledge on the structural and functional characteristics of the B-cell antigen receptor complex (BCR) and address the specific ability of accessory molecules to recruit intracellular signaling intermediates towards the activated receptor complex.