title: Autoinhibition and adapter function of Syk.
abstract: Development, survival, and activation of B lymphocytes are controlled by signals emanating from the B-cell antigen receptor (BCR). The BCR has an autonomous signaling function also known as tonic signaling that allows for long-term survival of B cells in the immune system. Upon binding of antigen to the BCR, the tonic signal is amplified and diversified, leading to alteration in gene expression and B-cell activation. The spleen tyrosine kinase (Syk) intimately cooperates with the signaling subunits of the BCR and plays a central role in the amplification and diversification of BCR signals. In this review, we discuss the molecular mechanisms by which Syk activity is inhibited and activated at the BCR. Importantly, Syk acts not only as a kinase that phosphorylates downstream substrates but also as an adapter that can bind to a diverse set of signaling proteins. Depending on its interactions and localization, Syk can signal opposing cell fate decisions such as proliferation or differentiation of B cells.
authors.affiliation: Centre for Biological Signaling Studies (Bioss) and Department of Molecular Immunology, Faculty of Biology, Albert-Ludwigs-Universität Freiburg and Max-Planck Institute for Immunobiology, Freiburg, Germany.
authors.forename: Yogesh
authors.initials: Y
authors.lastname: Kulathu
authors.forename: Gesina
authors.initials: G
authors.lastname: Grothe
authors.forename: Michael
authors.initials: M
authors.lastname: Reth
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D049109:Cell Proliferation; D006706:Homeostasis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D055503:Protein Multimerization / Q000276:immunology; D021122:Protein Subunits / Q000276:immunology / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000276:immunology / Q000378:metabolism*; D011947:Receptors, Antigen, B-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D000072377:Syk Kinase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D021122:Protein Subunits; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase