title: Complex phosphorylation dynamics control the composition of the Syk interactome in B cells.
abstract: Spleen tyrosine kinase Syk provides critical transducer functions for a number of immune cell receptors and has been implicated in the generation of several forms of leukemias. Catalytic activity and the ability of Syk to interact with other signaling elements depend on the phosphorylation status of Syk. We have now identified and quantified the full spectrum of phosphoacceptor sites in human Syk as well as the interactome of Syk in resting and activated B cells by high-resolution mass spectrometry. While the majority of inducible phosphorylations occurred on tyrosine residues, one of the most frequently detected phosphosites encompassed serine 297 located within the linker insert distinguishing the long and short isoforms of Syk. Full-length Syk can associate with more than 25 distinct ligands including the 14-3-3γ adaptor protein, which binds directly to phosphoserine 297. The latter complex attenuates inducible plasma membrane recruitment of Syk, thereby limiting antigen receptor-proximal signaling pathways. Collectively, the established ligand library provides a basis to understand the complexity of the Syk signaling network.
authors.affiliation: Georg August University of Göttingen, Institute of Cellular and Molecular Immunology, Humboldtallee, Göttingen, Germany.
authors.forename: Hanibal
authors.initials: H
authors.lastname: Bohnenberger
authors.forename: Thomas
authors.initials: T
authors.lastname: Oellerich
authors.forename: Michael
authors.initials: M
authors.lastname: Engelke
authors.forename: He-Hsuan
authors.initials: HH
authors.lastname: Hsiao
authors.forename: Henning
authors.initials: H
authors.lastname: Urlaub
authors.forename: Jürgen
authors.initials: J
authors.lastname: Wienands
mesh_terms: D048948:14-3-3 Proteins / Q000276:immunology / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020013:Calcium Signaling / Q000235:genetics; D002461:Cell Line, Transformed; D002645:Chickens; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000235:genetics; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D050505:Mutant Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D011485:Protein Binding / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D040901:Proteomics; D011940:Receptor Aggregation / Q000235:genetics; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D000072377:Syk Kinase
chemical_list: D048948:14-3-3 Proteins; D047908:Intracellular Signaling Peptides and Proteins; D050505:Mutant Proteins; D011947:Receptors, Antigen, B-Cell; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase