title: BLNK: molecular scaffolding through 'cis'-mediated organization of signaling proteins.
abstract: Assembly of intracellular macromolecular complexes is thought to provide an important mechanism to coordinate the generation of second messengers upon receptor activation. We have previously identified a B cell linker protein, termed BLNK, which serves such a scaffolding function in B cells. We demonstrate here that phosphorylation of five tyrosine residues within human BLNK nucleates distinct signaling effectors following B cell antigen receptor activation. The phosphorylation of multiple tyrosine residues not only amplifies PLCgamma-mediated signaling but also supports 'cis'-mediated interaction between distinct signaling effectors within a large molecular complex. These data demonstrate the importance of coordinate phosphorylation of molecular scaffolds, and provide insights into how assembly of macromolecular complexes is required for normal receptor function.
authors.affiliation: Center for Immunology, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Chiu
authors.forename: Mark
authors.initials: M
authors.lastname: Dalton
authors.forename: Masamichi
authors.initials: M
authors.lastname: Ishiai
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Chan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001665:Binding Sites; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051966:Phospholipase C gamma; D010750:Phosphoproteins / Q000502:physiology*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D002352:Carrier Proteins; D007527:Isoenzymes; D010750:Phosphoproteins; D011947:Receptors, Antigen, B-Cell; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium