Adaptors and linkers in T and B cells

By mediating non-covalent protein-protein interactions, adaptors organize and assemble the multimolecular signalling complexes that coordinate intracellular programs leading to the activation and differentiation of lymphocytes. The co-ordinated interaction between adaptor and effector molecules is required for the propagation and dynamic modification of externally applied signals. Recent advances have been made regarding our understanding of how adaptors regulate signalling within lymphocytes. An unexpected function has been revealed for the well-known adaptor protein LAT in pre-B-cell receptor signalling. In addition, the adaptors BCAP, Bcl10, CARMA1 and Malt1 seem to regulate the development of particular B-cell subsets. In contrast to Shc, c-Cbl and LAT, which are involved in early signalling events, BCAP, Bcl10, CARMA1 and Malt1 seem to act more distally, by controlling NF-kappaB activation. Additional transmembrane adaptors, such as NTAL/LAB and LIME, have been identified and partially characterized. Finally, an involvement of the cytosolic adaptors ADAP, SKAP-55 and Cbl-b in the regulation of lymphocyte adhesion and migration has been demonstrated.