HB-EGF–producing cells activate HER-1 signaling in MSCs. (A) Coculture of MSCs with cells that normally produce HB-EGF, such as LP1 myeloma cell line (membrane HB-EGF positive, soluble HB-EGF producing, and membrane HER-1 and HER-4 negative) led to a significant HER-1 phosphorylation in MSCs, compared with that observed using human recombinant HB-EGF (50 ng/mL), which is prevented by the use of blocking antibodies against HB-EGF (B). As phosphorylation is the event that triggers all HER-1–dependent intracellular activities,⁹  this evidence suggests that HB-EGF/HER-1 signaling may be operational in vivo. SSC indicates side scatter; FSC, forward scatter. Error bars indicate means ± SD of 3 different experiments.