| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 278, Issue 19, 16761-16769, May 9, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Sackler Institute for Muscular Skeletal Research,
Department of Medicine, University College London, 5 University
St., London WC1E 6JJ, United Kingdom
The widely expressed mammalian discoidin domain
receptors (DDRs), DDR1 and DDR2, are unique among receptor
tyrosine kinases in that they are activated by the extracellular matrix
protein collagen. Various collagen types bind to and activate the DDRs, but the molecular details of collagen recognition have not been well
defined. In this study, recombinant extracellular domains of DDR1 and
DDR2 were produced to explore DDR-collagen binding in detail. In solid
phase assays, both DDRs bound collagen I with high affinity. DDR1
recognized collagen I only as a dimeric and not as a monomeric
construct, indicating a requirement for receptor dimerization in the
DDR1-collagen interaction. The DDRs contain a discoidin homology domain
in their extracellular domains, and the isolated discoidin domain of
DDR2 bound collagen I with high affinity. Furthermore, the discoidin
domain of DDR2, but not of DDR1, was sufficient for transmembrane
receptor signaling. To map the collagen binding site within the
discoidin domain of DDR2, mutant constructs were created, in which
potential surface-exposed loops in DDR2 were exchanged for the
corresponding loops of functionally unrelated discoidin domains. Three
spatially adjacent surface loops within the DDR2 discoidin domain were
found to be critically involved in collagen binding of the isolated
DDR2 extracellular domain. In addition, the same loops were required
for collagen-dependent receptor activation. It is concluded
that the loop region opposite to the polypeptide chain termini of the
DDR2 discoidin domain constitutes the collagen recognition site.
Molecular Analysis of Collagen Binding by the Human Discoidin
Domain Receptors, DDR1 and DDR2
IDENTIFICATION OF COLLAGEN BINDING SITES IN DDR2*
*
This work was supported by an endowment of the Dr. Mortimer
and Mrs. Theresa Sackler Trust.The costs of publication of this article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed. Tel.: 44-20-7679-6167;
Fax: 44-20-7679-6219; E-mail: b.leitinger@ucl.ac.uk.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Kano, C. Marin de Evsikova, J. Young, C. Wnek, T. P. Maddatu, P. M. Nishina, and J. K. Naggert A Novel Dwarfism with Gonadal Dysfunction Due to Loss-of-Function Allele of the Collagen Receptor Gene, Ddr2, in the Mouse Mol. Endocrinol., August 1, 2008; 22(8): 1866 - 1880. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Abdulhussein, D. H. H. Koo, and W. F. Vogel Identification of Disulfide-linked Dimers of the Receptor Tyrosine Kinase DDR1 J. Biol. Chem., May 2, 2008; 283(18): 12026 - 12033. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Konitsiotis, N. Raynal, D. Bihan, E. Hohenester, R. W. Farndale, and B. Leitinger Characterization of High Affinity Binding Motifs for the Discoidin Domain Receptor DDR2 in Collagen J. Biol. Chem., March 14, 2008; 283(11): 6861 - 6868. [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]
|
|
|
|
|
|
S. J. Wall, E. Werner, Z. Werb, and Y. A. DeClerck Discoidin Domain Receptor 2 Mediates Tumor Cell Cycle Arrest Induced by Fibrillar Collagen J. Biol. Chem., December 2, 2005; 280(48): 40187 - 40194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Takada, R. N. Fariss, A. Tanikawa, Y. Zeng, D. Carper, R. Bush, and P. A. Sieving A Retinal Neuronal Developmental Wave of Retinoschisin Expression Begins in Ganglion Cells during Layer Formation Invest. Ophthalmol. Vis. Sci., September 1, 2004; 45(9): 3302 - 3312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Abdulhussein, C. McFadden, P. Fuentes-Prior, and W. F. Vogel Exploring the Collagen-binding Site of the DDR1 Tyrosine Kinase Receptor J. Biol. Chem., July 23, 2004; 279(30): 31462 - 31470. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
