Conformational plasticity and navigation of signaling proteins in antigen-activated B lymphocytes.
Over the past two decades our view of the B cell antigen receptor (BCR) has fundamentally changed. Being initially regarded as a mute antibody orphan of the B cell surface, the BCR turned out to be a complex multimolecular machine monitoring almost all stages of B cell development, selection, and activation through a plethora of ubiquitously and cell-type-specific effector proteins. A comprehensive understanding of the many BCR signaling facets is still out but a few common biochemical principles outlined in this review operate at the level of receptor activation and orchestrate specific wiring of intracellular transducer cascades. First, initiation and processing of antigen-induced signal transduction relies on transient conformational changes in the signaling proteins to trigger their physical interaction with downstream elements. Second, this dynamic assembly of signalosomes occurs at distinct subcellular locations, most prominently the plasma membrane, which requires dynamic relocalization of one or more of the engaged molecules. For both, precise complex formation and efficient subcellular targeting, B cell signaling components are equipped with a variety of protein interaction domains. Here we provide an overview on how these simple rules are applied by a limited number of transmembrane and cytosolic proteins to convert BCR ligation into Ca(2+) mobilization and Ras activation in an adjustable manner.
Engels
Niklas
N
Institute of Cellular and Molecular Immunology, Georg-August-University of Göttingen, 37073 Göttingen, Germany.
Engelke
Michael
M
Wienands
Jürgen
J
D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000502:physiology*; D008213:Lymphocyte Activation; D008954:Models, Biological; D011487:Protein Conformation; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
D047908:Intracellular Signaling Peptides and Proteins; D011947:Receptors, Antigen, B-Cell; D002118:Calcium