MISC

2004年2月

Dynamic regulation of Src-family kinases by CD45 in B cells

BLOOD
  • P Shrivastava
  • ,
  • T Katagiri
  • ,
  • M Ogimoto
  • ,
  • K Mizuno
  • ,
  • H Yakura

103
4
開始ページ
1425
終了ページ
1432
記述言語
英語
掲載種別
DOI
10.1182/blood-2003-03-0716
出版者・発行元
AMER SOC HEMATOLOGY

CD45 is a key protein tyrosine phosphatase regulating Src-famlly protein tyrosine kinases (Src-PTKs) in lymphocytes; precisely how it exerts its effect remains controversial, however. We previously demonstrated that CD45 negatively regulates Lyn in the WEHI-231 B-cell line. Here we show that negative regulation by CD45 is physiologically significant in B cells and that some CD45 is constitutively associated with glycolipid-enriched microdomains (GEMs), where it inhibits Src-PTKs by dephosphorylating both the negative and the positive regulatory sites. Upon B-cell receptor (BCR) ligation, however, CD45 dissociates from GEMs within 30 seconds, inducing phosphorylation of 2 regulatory sites and activation of Src-PTKs, but subsequently reassociates with the GEMs within 15 minutes. Disruption of GEMs with methyl-beta-cyclodextrin results in abrogation of BCR-induced apoptosis in WEHI-231 cells, suggesting GEMs are critical to signals leading to the fate determination. We propose that the primary function of CD45 is inhibition of Src-PTKs and that the level of SrcPTK activation and the B-cell fate are determined in part by dynamic behavior of CD45 with respect to GEMs.

Web of Science ® 被引用回数 : 30

リンク情報
DOI
https://doi.org/10.1182/blood-2003-03-0716
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000188828200043&DestApp=WOS_CPL

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