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© The Rockefeller University Press, 0021-9525/2003/9/751 $5.00
The Journal of Cell Biology, Volume 162, Number 5, 751-751

The healing power of Ron

Wounds heal more quickly with MSP (left). Santoro/Elsevier

A blood-localized growth factor hastens wound healing by pulling an integrin switcharoo on skin cells. The exchange, shown by Massimo Santoro (University of Piemonte Orientale, Novara, Italy) and colleagues, both releases adhered cells and promotes migration.

Skin cells stick to the basement membrane through hemidesmosome (HD)-localized integrin ₆ß₄. Santoro et al. show that the MSP growth factor releases ₆ß₄ from HDs and activates a migratory integrin, ₃ß₁, instead. Binding of MSP to its tyrosine kinase receptor, Ron, led to phosphorylation of both Ron and ₆ß₄, which introduced binding sites for 14-3-3 scaffolding proteins into both proteins. Through typical 14-3-3 dimerization, the phosphorylation thus creates a complex containing Ron and ₆ß₄.

MSP-induced Ron/integrin complexes were seen at the leading edge of migrating cells and corresponded with loss of ₆ß₄ from HDs. At the lamellipodia, phosphorylated ₆ß₄ switched to a signaling role. Along with Ron, ₆ß₄ activated transcription pathways that promote migration via production of matrix metalloproteases and additional MSP.

The venue change for ₆ß₄ had a ripple effect on another integrin. Before MSP stimulation, ₃ß₁, was stuck at cell–cell contacts, apparently in an inactive complex with Ron. But Ron exchanged partners upon phosphorylation, thus allowing ₃ß₁ to move to focal contacts, where it interacts with actin fibers to promote migration. This may explain why application of MSP to open wounds shortened the healing time for mice.

Reference:

Santoro, M., et al. 2003. Dev. Cell. 5:257–271.[CrossRef][Medline]

Nicole LeBrasseur

lebrasn{at}rockefeller.edu

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This Article PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by LeBrasseur, N. Search for Related Content PubMed Articles by LeBrasseur, N. Social Bookmarking                            What's this?