BLNK: a central linker protein in B cell activation.
Linker or adapter proteins provide mechanisms by which receptors can amplify and regulate downstream effector proteins. We describe here the identification of a novel B cell linker protein, termed BLNK, that interfaces the B cell receptor-associated Syk tyrosine kinase with PLCgamma, the Vav guanine nucleotide exchange factor, and the Grb2 and Nck adapter proteins. Tyrosine phosphorylation of BLNK by Syk provides docking sites for these SH2-containing effector molecules that, in turn, permits the phosphorylation and/or activation of their respective signaling pathways. Hence, BLNK represents a central linker protein that bridges the B cell receptor-associated kinases with a multitude of signaling pathways and may regulate the biologic outcomes of B cell function and development.
Center for Immunology, Program in Molecular Genetics, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
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Turck
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Kurosaki
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Chan
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary; D004792:Enzyme Precursors / Q000378:metabolism; D051380:GRB2 Adaptor Protein; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D051966:Phospholipase C gamma; D010750:Phosphoproteins; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011817:Rabbits; D017386:Sequence Homology, Amino Acid; D000072377:Syk Kinase; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C113939:B cell linker protein; D002352:Carrier Proteins; D018076:DNA, Complementary; D004792:Enzyme Precursors; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; C495949:Grb2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D010750:Phosphoproteins; D011506:Proteins; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D010738:Type C Phospholipases; D051966:Phospholipase C gamma