MMP14 encodes a membrane-tethered metalloproteinase MT1-MMP. The authors demonstrate that MT1-MMP forms a complex with FGFR2 and ADAM9 in osteoblasts and proteolytically inactivates ADAM9. This, in turn, protects FGFR2 from ADAM9-mediated ectodomain shedding on the cell surface. Mmp14−/− embryos have retarded parietal growth. This starts at 15.5 dpc and is attributable to impaired FGFR2 signaling due to increased shedding that is mediated by ADAM9. However, ADAM9 depletion completely rescued the defective FGFR2 signaling and largely restored calvarial bone growth in Mmp14−/− embryos.
Chan KM, Wong HL, Jin G, Liu B, Cao R, Cao Y, et al