Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 317 (5842): 1217-1220

Copyright © 2007 by the American Association for the Advancement of Science

Structure of a Tyrosine Phosphatase Adhesive Interaction Reveals a Spacer-Clamp Mechanism

A. Radu Aricescu,1* Christian Siebold,1* Kaushik Choudhuri,2 Veronica T. Chang,3 Weixian Lu,1 Simon J. Davis,3 P. Anton van der Merwe,2 E. Yvonne Jones1{dagger}

Abstract: Cell-cell contacts are fundamental to multicellular organisms and are subject to exquisite levels of control. Human RPTPµ is a type IIB receptor protein tyrosine phosphatase that both forms an adhesive contact itself and is involved in regulating adhesion by dephosphorylating components of cadherin-catenin complexes. Here we describe a 3.1 angstrom crystal structure of the RPTPµ ectodomain that forms a homophilic trans (antiparallel) dimer with an extended and rigid architecture, matching the dimensions of adherens junctions. Cell surface expression of deletion constructs induces intercellular spacings that correlate with the ectodomain length. These data suggest that the RPTPµ ectodomain acts as a distance gauge and plays a key regulatory function, locking the phosphatase to its appropriate functional location.

1 Cancer Research UK Receptor Structure Research Group, University of Oxford, Henry Wellcome Building of Genomic Medicine, Division of Structural Biology, Roosevelt Drive, Oxford OX3 7BN, UK.
2 Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE, UK.
3 Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, University of Oxford, Oxford OX3 9DS, UK.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: yvonne{at}

PTPs emerge as PIPs: protein tyrosine phosphatases with lipid-phosphatase activities in human disease.
R. Pulido, A. W. Stoker, and W. J. A. J. Hendriks (2013)
Hum. Mol. Genet. 22, R66-R76
   Abstract »    Full Text »    PDF »
Structural basis for angiopoietin-1-mediated signaling initiation.
X. Yu, T. C. M. Seegar, A. C. Dalton, D. Tzvetkova-Robev, Y. Goldgur, K. R. Rajashankar, D. B. Nikolov, and W. A. Barton (2013)
PNAS 110, 7205-7210
   Abstract »    Full Text »    PDF »
Structural basis for the sheddase function of human meprin {beta} metalloproteinase at the plasma membrane.
J. L. Arolas, C. Broder, T. Jefferson, T. Guevara, E. E. Sterchi, W. Bode, W. Stocker, C. Becker-Pauly, and F. X. Gomis-Ruth (2012)
PNAS 109, 16131-16136
   Abstract »    Full Text »    PDF »
Crystal structure of the Haemophilus influenzae Hap adhesin reveals an intercellular oligomerization mechanism for bacterial aggregation.
G. Meng, N. Spahich, R. Kenjale, G. Waksman, and J. W. St Geme III (2011)
EMBO J. 30, 3864-3874
   Abstract »    Full Text »    PDF »
Y. Xu, N. J. Kershaw, C. S. Luo, P. Soo, M. J. Pocock, P. E. Czabotar, D. J. Hilton, N. A. Nicola, T. P. J. Garrett, and J.-G. Zhang (2010)
J. Biol. Chem. 285, 21214-21218
   Abstract »    Full Text »    PDF »
The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules.
S. Bouyain and D. J. Watkins (2010)
PNAS 107, 2443-2448
   Abstract »    Full Text »    PDF »
Synapse formation regulated by protein tyrosine phosphatase receptor T through interaction with cell adhesion molecules and Fyn.
S.-H. Lim, S.-K. Kwon, M. K. Lee, J. Moon, D. G. Jeong, E. Park, S. J. Kim, B. C. Park, S. C. Lee, S.-E. Ryu, et al. (2009)
EMBO J. 28, 3564-3578
   Abstract »    Full Text »    PDF »
Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis.
A. J. Ramsay, J. D. Hooper, A. R. Folgueras, G. Velasco, and C. Lopez-Otin (2009)
Haematologica 94, 840-849
   Abstract »    Full Text »    PDF »
Mutational Inactivation of PTPRD in Glioblastoma Multiforme and Malignant Melanoma.
D. A. Solomon, J.-S. Kim, J. C. Cronin, Z. Sibenaller, T. Ryken, S. A. Rosenberg, H. Ressom, W. Jean, D. Bigner, H. Yan, et al. (2008)
Cancer Res. 68, 10300-10306
   Abstract »    Full Text »    PDF »
Tumor-Derived Extracellular Mutations of PTPRT/PTP{rho} Are Defective in Cell Adhesion.
J. Yu, S. Becka, P. Zhang, X. Zhang, S. M. Brady-Kalnay, and Z. Wang (2008)
Mol. Cancer Res. 6, 1106-1113
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882