論文

査読有り
2012年4月

Activation of receptor protein-tyrosine kinases from the cytoplasmic compartment

JOURNAL OF BIOCHEMISTRY
  • Yuji Yamanashi
  • ,
  • Tohru Tezuka
  • ,
  • Kazumasa Yokoyama

151
4
開始ページ
353
終了ページ
359
記述言語
英語
掲載種別
DOI
10.1093/jb/mvs013
出版者・発行元
OXFORD UNIV PRESS

It is widely accepted that receptor protein-tyrosine kinases (RTKs) are activated upon dimerization by binding to their extracellular ligands. However, EGF receptor (EGFR) dimerization per se does not require ligand binding. Instead, its cytoplasmic kinase domains have to form characteristic head-to-tail asymmetric dimers to become active, where one 'activator' domain activates the other 'receiver' domain. The non-catalytic, cytoplasmic regions of RTKs, namely the juxtamembrane and carboxy terminal portions, also regulate kinase activity. For instance, the juxtamembrane region of the RTK MuSK inhibits the kinase domain probably together with a cellular factor(s). These findings suggest that RTKs could be activated by cytoplasmic proteins. Indeed, Dok-7 and cytohesin have recently been identified as such activators of MuSK and EGFR, respectively. Given that failure of Dok-7 signaling causes myasthenia, and inhibition of cytohesin signaling reduces the proliferation of EGFR-dependent cancer cells, cytoplasmic activators of RTKs may provide new therapeutic targets.

リンク情報
DOI
https://doi.org/10.1093/jb/mvs013
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/22343747
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000302307100002&DestApp=WOS_CPL
ID情報
  • DOI : 10.1093/jb/mvs013
  • ISSN : 0021-924X
  • PubMed ID : 22343747
  • Web of Science ID : WOS:000302307100002

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