Activation of receptor protein-tyrosine kinases from the cytoplasmic compartment

Journal of Biochemistry
Yuji YamanashiKazumasa Yokoyama

Abstract

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.

References

May 17, 1996·Cell·D J GlassG D Yancopoulos
Mar 7, 1998·Genes & Development·S J Burden
Jun 1, 2001·Perception·A J Watkins
Nov 21, 2001·Nature Reviews. Neuroscience·J R Sanes, J W Lichtman
Aug 28, 2002·The Journal of Biological Chemistry·Jennifer StamosCharles Eigenbrot
May 3, 2003·Nature Reviews. Neuroscience·Andrew G EngelSteven M Sine
Nov 1, 2003·Annals of the New York Academy of Sciences·Angela VincentWerner Hoch
Jul 27, 2005·Proceedings of the National Academy of Sciences of the United States of America·Thomas MisgeldJoshua R Sanes
Dec 13, 2005·Molecular and Cellular Neurosciences·Boris A HesserVeit Witzemann
Jan 3, 2006·Current Opinion in Neurobiology·Terrance T KummerJoshua R Sanes
Jun 24, 2006·Science·Kumiko OkadaYuji Yamanashi
Aug 19, 2006·Science·David BeesonYuji Yamanashi
Dec 18, 2007·Nature Neuroscience·Natalie Kim, Steven J Burden
Jan 1, 2008·The Journal of Biological Chemistry·Johko HamuroYuji Yamanashi
Jul 16, 2008·Annals of Neurology·Duygu SelcenAndrew G Engel
Feb 27, 2009·Science Signaling·Akane InoueYuji Yamanashi
Mar 6, 2009·Journal of Medical Genetics·J VogtE R Maher
Nov 17, 2009·Immunological Reviews·Ryuichi MashimaYuji Yamanashi
Oct 16, 2010·Cell·Anke BillMichael Famulok
Nov 3, 2010·Genes & Development·Peter T HallockSteven J Burden
Apr 5, 2011·Breast Cancer Research : BCR·Carlos L Arteaga

❮ Previous
Next ❯

Citations

Jan 18, 2013·PloS One·Asma Ben AmmarDaniel Hantaï
Mar 10, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Huimin HuTao Jiang
Sep 25, 2012·Journal of Neuroimmunology·Masaharu TakamoriMasakatsu Motomura
Apr 1, 2015·PloS One·Elizabeth K ChangWeian Zhao
Sep 24, 2016·The American Journal of Pathology·Alejandro M GomezPilar Martinez-Martinez
Oct 7, 2017·International Journal of Food Sciences and Nutrition·D Brandão, L Ribeiro
Dec 21, 2012·Annals of the New York Academy of Sciences·Masaharu Takamori
Aug 15, 2019·Molecular Biology of the Cell·Natasha KoppelSteven J Burden
Mar 8, 2019·The Journal of Cell Biology·Julien OurySteven J Burden
Aug 1, 2012·Journal of Signal Transduction·Vasanthy VigneswaraZubair Ahmed
Jul 1, 2016·Physiological Reviews·Jianchun ChenRaymond C Harris

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Signaling by Tyrosine Kinases

Receptor tyrosine kinases (RTKs) are the high-affinity cell surface receptors for many polypeptide growth factors, cytokines, and hormones. RTKs have been shown not only to be key regulators of normal cellular processes but also to have a critical role in the development and progression of many types of cancer. Discover the latest research on cell signaling and RTK here.