![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Vol. 13, Issue 7, 2547-2557, July 2002
*Department of Cell Biology, Research Institute for Microbial
Diseases, Osaka University, Suita, Osaka 565-0871, Japan, and
Dimerization and phosphorylation of the epidermal growth factor
(EGF) receptor (EGFR) are the initial and essential events of
EGF-induced signal transduction. However, the mechanism by which EGFR
ligands induce dimerization and phosphorylation is not fully
understood. Here, we demonstrate that EGFRs can form dimers on the cell
surface independent of ligand binding. However, a chimeric receptor,
comprising the extracellular and transmembrane domains of EGFR and the
cytoplasmic domain of the erythropoietin receptor (EpoR), did not form
a dimer in the absence of ligands, suggesting that the cytoplasmic
domain of EGFR is important for predimer formation. Analysis of
deletion mutants of EGFR showed that the region between
835Ala and 918Asp of the EGFR cytoplasmic
domain is required for EGFR predimer formation. In contrast to
wild-type EGFR ligands, a mutant form of heparin-binding EGF-like
growth factor (HB2) did not induce dimerization of the EGFR-EpoR
chimeric receptor and therefore failed to activate the chimeric
receptor. However, when the dimerization was induced by a monoclonal
antibody to EGFR, HB2 could activate the chimeric receptor. These
results indicate that EGFR can form a ligand-independent inactive dimer
and that receptor dimerization and activation are mechanistically
distinct and separable events.
Institute of Life Science, Kurume University, Kurume,
Fukuoka 839-0861, Japan
Corresponding author. E-mail address:
emekada{at}biken.osaka-u.ac.jp.
This article has been cited by other articles:
|
|
 |
|
  H. Mizushima, X. Wang, S. Miyamoto, and E. Mekada Integrin signal masks growth-promotion activity of HB-EGF in monolayer cell cultures J. Cell Sci., December 1, 2009; 122(23): 4277 - 4286. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ding, H. Komatsu, S. Iida, H. Yano, S. Kusumoto, A. Inagaki, F. Mori, M. Ri, A. Ito, A. Wakita, et al. The Asn505 mutation of the c-MPL gene, which causes familial essential thrombocythemia, induces autonomous homodimerization of the c-Mpl protein due to strong amino acid polarity Blood, October 8, 2009; 114(15): 3325 - 3328. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Zhang, Y. Jiang, Q. Wang, X. Ma, Z. Xiao, W. Zuo, X. Fang, and Y.-G. Chen Single-molecule imaging reveals transforming growth factor-{beta}-induced type II receptor dimerization PNAS, September 15, 2009; 106(37): 15679 - 15683. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. Yang, Ma. X. G. Ilagan, D. Piwnica-Worms, and L. J. Pike Luciferase Fragment Complementation Imaging of Conformational Changes in the Epidermal Growth Factor Receptor J. Biol. Chem., March 20, 2009; 284(12): 7474 - 7482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.-H. Tao and I. N. Maruyama All EGF(ErbB) receptors have preformed homo- and heterodimeric structures in living cells J. Cell Sci., October 1, 2008; 121(19): 3207 - 3217. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. E. Cavet, E. M. Smolock, O. H. Ozturk, C. World, J. Pang, A. Konishi, and B. C. Berk Gas6-Axl Receptor Signaling Is Regulated by Glucose in Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, May 1, 2008; 28(5): 886 - 891. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Lammerts van Bueren, W. K. Bleeker, A. Brannstrom, A. von Euler, M. Jansson, M. Peipp, T. Schneider-Merck, T. Valerius, J. G. J. van de Winkel, and P. W. H. I. Parren The antibody zalutumumab inhibits epidermal growth factor receptor signaling by limiting intra- and intermolecular flexibility PNAS, April 22, 2008; 105(16): 6109 - 6114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Mahtani and J. S. Macdonald Synergy Between Cetuximab and Chemotherapy in Tumors of the Gastrointestinal Tract Oncologist, January 1, 2008; 13(1): 39 - 50. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Ali, K. V. S. K. Prasad, I. Day, and A. S. N. Reddy Ligand-Dependent Reduction in the Membrane Mobility of FLAGELLIN SENSITIVE2, an Arabidopsis Receptor-Like Kinase Plant Cell Physiol., November 1, 2007; 48(11): 1601 - 1611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. K. Gan, F. Walker, A. W. Burgess, A. Rigopoulos, A. M. Scott, and T. G. Johns The Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitor AG1478 Increases the Formation of Inactive Untethered EGFR Dimers: IMPLICATIONS FOR COMBINATION THERAPY WITH MONOCLONAL ANTIBODY 806 J. Biol. Chem., February 2, 2007; 282(5): 2840 - 2850. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. L. Gadd and C. V. Clevenger Ligand-Independent Dimerization of the Human Prolactin Receptor Isoforms: Functional Implications Mol. Endocrinol., November 1, 2006; 20(11): 2734 - 2746. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Noordeen, F. Carafoli, E. Hohenester, M. A. Horton, and B. Leitinger A Transmembrane Leucine Zipper Is Required for Activation of the Dimeric Receptor Tyrosine Kinase DDR1 J. Biol. Chem., August 11, 2006; 281(32): 22744 - 22751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. A. Clayton, F. Walker, S. G. Orchard, C. Henderson, D. Fuchs, J. Rothacker, E. C. Nice, and A. W. Burgess Ligand-induced Dimer-Tetramer Transition during the Activation of the Cell Surface Epidermal Growth Factor Receptor-A Multidimensional Microscopy Analysis J. Biol. Chem., August 26, 2005; 280(34): 30392 - 30399. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wang, M. B. Goshe, E. J. Soderblom, B. S. Phinney, J. A. Kuchar, J. Li, T. Asami, S. Yoshida, S. C. Huber, and S. D. Clouse Identification and Functional Analysis of in Vivo Phosphorylation Sites of the Arabidopsis BRASSINOSTEROID-INSENSITIVE1 Receptor Kinase PLANT CELL, June 1, 2005; 17(6): 1685 - 1703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kani, C. M. Warren, C. S. Kaddis, J. A. Loo, and R. Landgraf Oligomers of ERBB3 Have Two Distinct Interfaces That Differ in Their Sensitivity to Disruption by Heregulin J. Biol. Chem., March 4, 2005; 280(9): 8238 - 8247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ahr, M. Denizot, V. Robert-Hebmann, A. Brelot, and M. Biard-Piechaczyk Identification of the Cytoplasmic Domains of CXCR4 Involved in Jak2 and STAT3 Phosphorylation J. Biol. Chem., February 25, 2005; 280(8): 6692 - 6700. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Takazaki, Y. Shishido, R. Iwamoto, and E. Mekada Suppression of the Biological Activities of the Epidermal Growth Factor (EGF)-like Domain by the Heparin-binding Domain of Heparin-binding EGF-like Growth Factor J. Biol. Chem., November 5, 2004; 279(45): 47335 - 47343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liu, R. Li, and S. Ladisch Exogenous Ganglioside GD1a Enhances Epidermal Growth Factor Receptor Binding and Dimerization J. Biol. Chem., August 27, 2004; 279(35): 36481 - 36489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Walker, S. G. Orchard, R. N. Jorissen, N. E. Hall, H.-H. Zhang, P. A. Hoyne, T. E. Adams, T. G. Johns, C. Ward, T. P. J. Garrett, et al. CR1/CR2 Interactions Modulate the Functions of the Cell Surface Epidermal Growth Factor Receptor J. Biol. Chem., May 21, 2004; 279(21): 22387 - 22398. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Odintsova, J. Voortman, E. Gilbert, and F. Berditchevski Tetraspanin CD82 regulates compartmentalisation and ligand-induced dimerization of EGFR J. Cell Sci., November 15, 2003; 116(22): 4557 - 4566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q.-C. Cheng, O. Tikhomirov, W. Zhou, and G. Carpenter Ectodomain Cleavage of ErbB-4: CHARACTERIZATION OF THE CLEAVAGE SITE AND m80 FRAGMENT J. Biol. Chem., October 3, 2003; 278(40): 38421 - 38427. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Brown, N. Hu, and J. C.-G. Hombria Novel level of signalling control in the JAK/STAT pathway revealed by in situ visualisation of protein-protein interaction during Drosophila development Development, July 15, 2003; 130(14): 3077 - 3084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. S. Hendriks, L. K. Opresko, H. S. Wiley, and D. Lauffenburger Quantitative Analysis of HER2-mediated Effects on HER2 and Epidermal Growth Factor Receptor Endocytosis: DISTRIBUTION OF HOMO- AND HETERODIMERS DEPENDS ON RELATIVE HER2 LEVELS J. Biol. Chem., June 20, 2003; 278(26): 23343 - 23351. [Abstract] [Full Text] [PDF]
|
|
