Structural aspects of signal transduction in B-cells

Signal transduction in hematopoietic cells is a highly specific process. The stimulation of B cell receptor following antigen binding triggers, as a first step, phosphorylation of the cytoplasmic immunoreceptor tyrosine-based activation motifs (ITAMs). Src family tyrosine kinases Blk, Fyn, Lck, and Lyn as well as spleen kinase, Syk, are activated to transmit the signal further. In this review the signaling events are discussed in structural terms. The factors related to B cell maturation and their targeted mutations are reviewed. During the last 2 years plenty of structural information concerning signaling molecules in B cells has been obtained by using X-ray crystallography, NMR spectroscopy, molecular modeling, and mutational analysis. The molecules discussed include Src family kinases, Syk, Grb2 adaptor protein, and Tec family kinases Bmx and Btk. The structure, function, and interactions of these signaling compounds are described in atomic detail.