Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 4445K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Tolg, C. Articles by Turley, E. A. Search for Related Content PubMed PubMed Citation Articles by Tolg, C. Articles by Turley, E. A. Social Bookmarking                            What's this?

Rhamm^–/– fibroblasts are defective in CD44-mediated ERK1,2 motogenic signaling, leading to defective skin wound repair

¹ London Regional Cancer Program, London, Ontario N6A 4L6, Canada
² Department of Biochemistry, ³ Department of Anatomy and Cell Biology, and ⁴ Department of Oncology, University of Western Ontario, London, Ontario N6A 5B8, Canada
⁵ Connective Tissue Research Group, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada
⁶ Department of Laboratory Medicine and Pathology and Comprehensive Cancer Center, University of Minnesota, Minneapolis, MN 55455
⁷ Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720

Correspondence to Eva A. Turley: eva.turley{at}lhsc.on.ca

Rhamm (receptor for hyaluronan-mediated motility) is an hyaluronan binding protein with limited expression in normal tissues and high expression in advanced cancers. To understand its physiological functions and identify the molecular mechanisms underlying these functions, we created mice with a genetic deletion of Rhamm. We show that Rhamm^–/– fibroblasts fail to resurface scratch wounds >3 mm or invade hyaluronan-supplemented collagen gels in culture. We identify a requirement for Rhamm in the localization of CD44 to the cell surface, formation of CD44–ERK1,2 (extracellular-regulated kinase 1,2) complexes, and activation/subcellular targeting of ERK1,2 to the cell nucleus. We also show that cell surface Rhamm, restricted to the extracellular compartment by linking recombinant protein to beads, and expression of mutant active mitogen-activated kinase kinase 1 (Mek1) are sufficient to rescue aberrant signaling through CD44–ERK1,2 complexes in Rh^–/– fibroblasts. ERK1,2 activation and fibroblast migration/differentiation is also defective during repair of Rh^–/– excisional skin wounds and results in aberrant granulation tissue in vivo. These results identify Rhamm as an essential regulator of CD44–ERK1,2 fibroblast motogenic signaling required for wound repair.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

• Maxwell, C. A., McCarthy, J., Turley, E. (2008). Cell-surface and mitotic-spindle RHAMM: moonlighting or dual oncogenic functions?. J. Cell Sci. 121: 925-932 [Abstract] [Full Text]  
• Hamilton, S. R., Fard, S. F., Paiwand, F. F., Tolg, C., Veiseh, M., Wang, C., McCarthy, J. B., Bissell, M. J., Koropatnick, J., Turley, E. A. (2007). The Hyaluronan Receptors CD44 and Rhamm (CD168) Form Complexes with ERK1,2 That Sustain High Basal Motility in Breast Cancer Cells. J. Biol. Chem. 282: 16667-16680 [Abstract] [Full Text]  
• Tolg, C., Hamilton, S. R., Nakrieko, K.-A., Kooshesh, F., Walton, P., McCarthy, J. B., Bissell, M. J., Turley, E. A. (2006). Rhamm-/- fibroblasts are defective in CD44-mediated ERK1,2 motogenic signaling, leading to defective skin wound repair. JEM 203: i31-31 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents