Molecules and Cells

, Volume 29, Issue 5, pp 443–448

Asymmetric tyrosine kinase arrangements in activation or autophosphorylation of receptor tyrosine kinases

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DOI: 10.1007/s10059-010-0080-5

Cite this article as:
Bae, J.H. & Schlessinger, J. Mol Cells (2010) 29: 443. doi:10.1007/s10059-010-0080-5

Abstract

Receptor tyrosine kinases (RTKs) play important roles in the control of many cellular processes including cell proliferation, cell adhesion, angiogenesis, and apoptosis. Ligand-induced dimerization of RTKs leads to autophosphorylation and activation of RTKs. Structural studies have shown that while isolated ectodomains of several RTKs form symmetric dimers the isolated cytoplasmic kinase domains of epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR) form asymmetric dimers during their activation. Binding of one kinase molecule of EGFR to a second kinase molecule asymmetrically leads to stimulation of kinase activity and enhanced autophosphorylation. Furthermore, the structures of the kinase domain of FGFR1 and FGFR2 reveal the formation of asymmetric interfaces in the processes of autophosphorylation at their specific phosphotyrosine (pY) sites. Disruption of asymmetric dimer interface of EGFR leads to reduction in enzymatic activity and drastic reduction of autophosphorylation of FGFRs in ligandstimulated live cells. These studies demonstrate that asymmetric dimer formation is as a common phenomenon critical for activation and autophosphorylation of RTKs.

Keywords

asymmetriccell signalingphosphorylationprotein kinasex-ray crystallography

Copyright information

© The Korean Society for Molecular and Cellular Biology and Springer Netherlands 2010

Authors and Affiliations

  1. 1.Department of PharmacologyYale University School of MedicineNew HavenUSA