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Santoro/Elsevier* y' i: Q- L9 z% k3 r. V( `3 t- h8 c
- a% h) C9 D9 Z- Q* NA 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." X* @4 o# W, o6 s% d% Q
0 t1 W' I( A* m# g9 \* ^Skin cells stick to the basement membrane through hemidesmosome (HD)-localized integrin 6?4. Santoro et al. show that the MSP growth factor releases 6?4 from HDs and activates a migratory integrin, 3?1, instead. Binding of MSP to its tyrosine kinase receptor, Ron, led to phosphorylation of both Ron and 6?4, 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 6?4.
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6 _; X8 G0 \; ~$ f2 l& M8 S+ l4 {MSP-induced Ron/integrin complexes were seen at the leading edge of migrating cells and corresponded with loss of 6?4 from HDs. At the lamellipodia, phosphorylated 6?4 switched to a signaling role. Along with Ron, 6?4 activated transcription pathways that promote migration via production of matrix metalloproteases and additional MSP.. m4 H. a2 Z% |7 }, E, z
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The venue change for 6?4 had a ripple effect on another integrin. Before MSP stimulation, 3?1, was stuck at cell–cell contacts, apparently in an inactive complex with Ron. But Ron exchanged partners upon phosphorylation, thus allowing 3?1 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.% T1 {9 @( g4 {9 E
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, V/ C" U7 t" Z! p* `Santoro, M., et al. 2003. Dev. Cell. 5:257–271.(Wounds heal more quickly with MSP (left)) |
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