國家衛生研究院 NHRI:Item 3990099045/6251
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    NHRI > Immunology Research Center > Tse-Hua Tan > Periodical Articles >  Item 3990099045/6251


    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/6251


    Title: Down-regulation of B-cell receptor signaling by hematopoietic progenitor kinase 1 (HPK1)-mediated phosphorylation and Ubiquitination of the activated B cell linker protein (BLNK)
    Authors: Wang, X;Li, JP;Kuo, HK;Chu, LL;Dement, GA;Lan, JL;Chen, DY;Yang, CY;Hu, H;Tan, TH
    Contributors: Immunology Research Center
    Abstract: Hematopoietic progenitor kinase 1 (HPK1) is a Ste20-like serine/threonine kinase that suppresses immune responses and autoimmunity. B-cell receptor (BCR) signaling activates HPK1 by inducing BLNK/HPK1 interaction. Whether HPK1 can reciprocally regulate BLNK during BCR signaling is unknown. Here we show that HPK1-deficient B cells display hyper-proliferation and hyper-activation of IKK and MAPKs (ERK, p38, and JNK) upon the ligation of BCR. HPK1 attenuates BCR-induced cell activation via inducing BLNK threonine152 phosphorylation, which mediates BLNK/14-3-3 binding. Furthermore, threonine152-phosphorylated BLNK is ubiquitinated at lysine37, 38 and 42 residues, leading to attenuation of MAPK and IKK activation in B cells during BCR signaling. These results reveal a novel negative feedback regulation of BCR signaling by HPK1-mediated phosphorylation, ubiquitination, and subsequent degradation of the activated BLNK.
    Date: 2012-03
    Relation: Journal of Biological Chemistry. 2012 Mar;287(14):11037-11048.
    Link to: http://dx.doi.org/10.1074/jbc.M111.310946
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1083-351X&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000302780100032
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84859514199
    Appears in Collections:[Tse-Hua Tan] Periodical Articles

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