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Role of the rasGAP-associated docking protein p62^(dok) in negative regulation of B cell receptor-mediated signaling

Yamanashi, Yuji and Tamura, Toshiki and Kanamori, Toshihide and Yamane, Hidehiro and Nariuchi, Hideo and Yamamoto, Tadashi and Baltimore, David (2000) Role of the rasGAP-associated docking protein p62^(dok) in negative regulation of B cell receptor-mediated signaling. Genes and Development, 14 (1). pp. 11-16. ISSN 0890-9369. PMCID PMC316343. doi:10.1101/gad.14.1.11.

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Antigenic stimulation of the B-cell receptor (BCR) is a central event in the immune response. In contrast, antigen bound to IgG negatively regulates signals from the BCR by cross-linking it to the inhibitory receptor FcγRIIB. Here we show that upon cross-linking of BCR or BCR with FcγRIIB, the rasGAP-associated protein p62^(dok) is prominently tyrosine phosphorylated in a Lyn-dependent manner. Inactivation of the dok gene by homologous recombination has shown that upon BCR cross-linking, p62^(dok) suppresses MAP kinase and is indispensable for FcγRIIB-mediated negative regulation of cell proliferation. We propose that p62^(dok), a downstream target of many PTKs, plays a negative role in various signaling situations.

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Baltimore, David0000-0001-8723-8190
Additional Information:© 2000 by Cold Spring Harbor Laboratory Press. Received September 27, 1999; revised version accepted November 18, 1999. We thank M. Scott, J. Harrison, A. Koleske, E. Brown, and P. Svec for help in generating dok^(+/−) mice, and members of the animal facilities of both Massachusetts Institute of Technology and Institute of Medical Science (University of Tokyo) for animal care. We also thank S. Tronick and J. Ravetch for antibodies and K. Horikawa, H. Nishizumi, H. Yoshida, B. Chen, G. Cohen, C. Lois, C. Roman, B. Horwitz and other members of the Baltimore, Yamamoto, and Nariuch laboratories for helpful discussions during the course of this work. Y.Y. thanks S. Nishikawa and K. Toyoshima for discussion and encouragement. This work was supported by a U.S. Public Health Service research grant (D.B.) and by grants from the Ministry of Education, Sciences, Sports, and Culture of Japan (Y.Y., H.N., and T.Y.). The publication costs of this article were defrayed in part by payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 USC section 1734 solely to indicate this fact.
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Ministry of Education, Culture, Sports, Science and Technology (MEXT)UNSPECIFIED
Subject Keywords:Dok; Lyn; B cell receptor; FcgRIIB; tyrosine kinase; MAP kinase
Issue or Number:1
PubMed Central ID:PMC316343
Record Number:CaltechAUTHORS:20200506-142242679
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:103047
Deposited By: Tony Diaz
Deposited On:06 May 2020 21:39
Last Modified:16 Nov 2021 18:17

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