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.

Science 19 August 2005:
Vol. 309. no. 5738, pp. 1256 - 1259
DOI: 10.1126/science.1112521
Prev | Table of Contents | Next

Reports

Mitogenic Influence of Human R-Spondin1 on the Intestinal Epithelium

Kyung-Ah Kim,1* Makoto Kakitani,2 Jingsong Zhao,1 Takeshi Oshima,2 Tom Tang,1 Minke Binnerts,1 Yi Liu,1 Bryan Boyle,1 Emily Park,1 Peter Emtage,1 Walter D. Funk,1{dagger} Kazuma Tomizuka2*{dagger}

Several described growth factors influence the proliferation and regeneration of the intestinal epithelium. Using a transgenic mouse model, we identified a human gene, R-spondin1, with potent and specific proliferative effects on intestinal crypt cells. Human R-spondin1 (hRSpo1) is a thrombospondin domain-containing protein expressed in enteroendocrine cells as well as in epithelial cells in various tissues. Upon injection into mice, the protein induced rapid onset of crypt cell proliferation involving ß-catenin stabilization, possibly by a process that is distinct from the canonical Wnt-mediated signaling pathway. The protein also displayed efficacy in a model of chemotherapy-induced intestinal mucositis and may have therapeutic application in gastrointestinal diseases.

1 Nuvelo, Inc., 675 Almanor Avenue, Sunnyvale, CA 94085, USA.
2 Pharmaceutical Research Laboratories, Pharmaceutical Division, Kirin Brewery Co., Ltd., 3 Miyahara-cho, Takasaki-shi, Gunma 370-1295, Japan.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: wfunk{at}nuvelo.com (W.D.F.); ktomizuka{at}kirin.co.jp (K.T.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
R-Spondin1 protects mice from chemotherapy or radiation-induced oral mucositis through the canonical Wnt/{beta}-catenin pathway.
J. Zhao, K.-A. Kim, J. De Vera, S. Palencia, M. Wagle, and A. Abo (2009)
PNAS 106, 2331-2336
   Abstract »    Full Text »    PDF »
The Wnt signaling regulator R-spondin 3 promotes angioblast and vascular development.
O. Kazanskaya, B. Ohkawara, M. Heroult, W. Wu, N. Maltry, H. G. Augustin, and C. Niehrs (2008)
Development 135, 3655-3664
   Abstract »    Full Text »    PDF »
Formation of the blood-brain barrier: Wnt signaling seals the deal.
P. Polakis (2008)
J. Cell Biol. 183, 371-373
   Abstract »    Full Text »    PDF »
R-Spondin Family Members Regulate the Wnt Pathway by a Common Mechanism.
K.-A. Kim, M. Wagle, K. Tran, X. Zhan, M. A. Dixon, S. Liu, D. Gros, W. Korver, S. Yonkovich, N. Tomasevic, et al. (2008)
Mol. Biol. Cell 19, 2588-2596
   Abstract »    Full Text »    PDF »
R-spondin1 plays an essential role in ovarian development through positively regulating Wnt-4 signaling.
K. Tomizuka, K. Horikoshi, R. Kitada, Y. Sugawara, Y. Iba, A. Kojima, A. Yoshitome, K. Yamawaki, M. Amagai, A. Inoue, et al. (2008)
Hum. Mol. Genet. 17, 1278-1291
   Abstract »    Full Text »    PDF »
Activation of {beta}-catenin signaling by Rspo1 controls differentiation of the mammalian ovary.
A.-A. Chassot, F. Ranc, E. P. Gregoire, H. L. Roepers-Gajadien, M. M. Taketo, G. Camerino, D. G. de Rooij, A. Schedl, and M.-C. Chaboissier (2008)
Hum. Mol. Genet. 17, 1264-1277
   Abstract »    Full Text »    PDF »
Glucagon-Like Peptide-2 Activates -Catenin Signaling in the Mouse Intestinal Crypt: Role of Insulin-Like Growth Factor-I.
P. E. Dube, K. J. Rowland, and P. L. Brubaker (2008)
Endocrinology 149, 291-301
   Abstract »    Full Text »    PDF »
The Role of Matrix Metalloproteinases in Stromal/Epithelial Interactions in the Gut.
N. Sengupta and T. T. MacDonald (2007)
Physiology 22, 401-409
   Abstract »    Full Text »    PDF »
R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6.
M. E. Binnerts, K.-A. Kim, J. M. Bright, S. M. Patel, K. Tran, M. Zhou, J. M. Leung, Y. Liu, W. E. Lomas III, M. Dixon, et al. (2007)
PNAS 104, 14700-14705
   Abstract »    Full Text »    PDF »
R-spondin1 Is a High Affinity Ligand for LRP6 and Induces LRP6 Phosphorylation and beta-Catenin Signaling.
Q. Wei, C. Yokota, M. V. Semenov, B. Doble, J. Woodgett, and X. He (2007)
J. Biol. Chem. 282, 15903-15911
   Abstract »    Full Text »    PDF »
Selection of Early-Occurring Mutations Dictates Hormone-Independent Progression in Mouse Mammary Tumor Lines.
A. Gattelli, M. N. Zimberlin, R. P. Meiss, L. H. Castilla, and E. C. Kordon (2006)
J. Virol. 80, 11409-11415
   Abstract »    Full Text »    PDF »
A WNTer wonderland in Snowbird..
X. He and J. D. Axelrod (2006)
Development 133, 2597-2603
   Abstract »    Full Text »    PDF »
Mouse Cristin/R-spondin Family Proteins Are Novel Ligands for the Frizzled 8 and LRP6 Receptors and Activate beta-Catenin-dependent Gene Expression.
J.-S. Nam, T. J. Turcotte, P. F. Smith, S. Choi, and J. K. Yoon (2006)
J. Biol. Chem. 281, 13247-13257
   Abstract »    Full Text »    PDF »
Inducing Intestinal Growth..
C. Abraham and J. H. Cho (2005)
N. Engl. J. Med. 353, 2297-2299
   Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)