Strong oligomerization behavior of PDGFβ receptor transmembrane domain and its regulation by the juxtamembrane regions
Oates, Joanne, King, G. (Gavin) and Dixon, Ann M.. (2010) Strong oligomerization behavior of PDGFβ receptor transmembrane domain and its regulation by the juxtamembrane regions. Biochimica et Biophysica Acta (BBA) - Biomembranes, Vol.1798 (No.3). pp. 605-615. ISSN 00052736Full text not available from this repository.
Official URL: http://dx.doi.org/10.1016/j.bbamem.2009.12.016
The platelet-derived growth factor P-receptor (PDGF beta R) represents an important subclass of receptor tyrosine kinase (RTK) thought to be activated by ligand-induced dimerization. Interestingly, the receptor is also activated by the bovine papillomavirus E5 oncoprotein, an interaction involving the transmembrane domains of both proteins and resulting in constitutive downstream signalling. This unique mode of activation along with emerging data for other RTKs raises important questions about the role of the PDGF beta R transmembrane domain in signalling. To address this, we have investigated the murine PDGF beta R transmembrane and juxtamembrane domains. We show for the first time the strong oligomerization behavior of PDGF beta R transmembrane domain, forming dimers and trimers in natural membranes and detergents; and that these self-interactions are mediated by a leucine-zipper-like motif. The juxtamembrane regions are found to regulate these helix-helix interactions and select specifically for dimer formation. These data provide evidence that PDGF beta R is able to form ligand-independent dimers, supporting similar observations in a number of other RTK's. A point mutant in the PDGF beta R juxtamembrane domain previously shown to cause receptor activation was studied and yielded no change in oligomerization or folding, suggesting (in-line with observations of the c-Kit receptor) that it may moderate interactions with other regions of PDGF beta R. (C) 2010 Elsevier B.V. All rights reserved.
|Item Type:||Journal Article|
|Subjects:||Q Science > QD Chemistry
Q Science > QP Physiology
|Divisions:||Faculty of Science > Chemistry|
|Library of Congress Subject Headings (LCSH):||Cellular signal transduction, Ultracentrifugation, Platelet-derived growth factor, Cell receptors|
|Journal or Publication Title:||Biochimica et Biophysica Acta (BBA) - Biomembranes|
|Number of Pages:||11|
|Page Range:||pp. 605-615|
|Access rights to Published version:||Restricted or Subscription Access|
|Funder:||Cancer Research UK|
|Grant number:||C21449/A6926 (CRUK)|
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