title: Tyrosine phosphorylation of 3BP2 is indispensable for the interaction with VAV3 in chicken DT40 cells.
abstract: Adaptor protein c-Abl SH3 domain-binding protein-2 (3BP2) is known to play regulatory roles in immunoreceptor-mediated signal transduction. We have previously demonstrated that Tyr(174), Tyr(183) and Tyr(446) in mouse 3BP2 are predominantly phosphorylated by Syk, and the phosphorylation of Tyr(183) and the Src homology 2 (SH2) domain of mouse 3BP2 are critical for B cell receptor (BCR)-induced activation of nuclear factor of activated T cells (NFAT) in human B cells. In this report, we have shown that Syk, but not Abl family protein-tyrosine kinases, is critical for BCR-mediated tyrosine phosphorylation of 3BP2 in chicken DT40 cells. Mutational analysis showed that Tyr(174), Tyr(183) and Tyr(426) of chicken 3BP2 are the major phosphorylation sites by Syk and the SH2 domain of 3BP2 is critical for tyrosine phosphorylation. In addition, phosphorylation of Tyr(426) is required for the inducible interaction with the SH2 domain of Vav3. Moreover, the expression of the mutant form of 3BP2 in which Tyr(426) was substituted to Phe resulted in the reduction in BCR-mediated Rac1 activation, when compared with the case of wild-type. Altogether, these data suggest that 3BP2 is involved in the activation of Rac1 through the regulation of Vav3 by Syk-dependent phosphorylation of Tyr(426) following BCR stimulation.
authors.affiliation: Division of Genome Science and Microbiology, Department of Pathological Sciences, Faculty of Medical Sciences, Fukui 910-1193, Japan; Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Kazuyasu
authors.initials: K
authors.lastname: Chihara
authors.affiliation: Division of Genome Science and Microbiology, Department of Pathological Sciences, Faculty of Medical Sciences, Fukui 910-1193, Japan; Division of Otorhinolaryngology Head and Neck Surgery, Department of Sensory and Locomotor Medicine, Faculty of Medical Sciences, Fukui 910-1193, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Kimura
authors.affiliation: Division of Genome Science and Microbiology, Department of Pathological Sciences, Faculty of Medical Sciences, Fukui 910-1193, Japan; Third Department of Internal Medicine, Faculty of Medical Sciences, Fukui 910-1193, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Honjoh
authors.affiliation: Division of Genome Science and Microbiology, Department of Pathological Sciences, Faculty of Medical Sciences, Fukui 910-1193, Japan; Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Shota
authors.initials: S
authors.lastname: Yamauchi
authors.affiliation: Division of Genome Science and Microbiology, Department of Pathological Sciences, Faculty of Medical Sciences, Fukui 910-1193, Japan; Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Division of Genome Science and Microbiology, Department of Pathological Sciences, Faculty of Medical Sciences, Fukui 910-1193, Japan; Organization for Life Science Advancement Programs, University of Fukui, Fukui 910-1193, Japan. Electronic address: ksada@u-fukui.ac.jp.
authors.forename: Kiyonao
authors.initials: K
authors.lastname: Sada
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002645:Chickens; D002522:Chlorocebus aethiops; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D010766:Phosphorylation / Q000502:physiology; D011485:Protein Binding; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051562:Proto-Oncogene Proteins c-bcr / Q000378:metabolism; D051567:Proto-Oncogene Proteins c-vav / Q000378:metabolism*; D000072377:Syk Kinase; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D051567:Proto-Oncogene Proteins c-vav; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D051562:Proto-Oncogene Proteins c-bcr
keywords: 3BP2; Abl; Adaptor proteins; B cell receptor; Syk; Vav3