Fig. 7
Schematic depicting the role of IgSF11-mediated regulation of PKM2 activity during osteoclast differentiation. a PKM2 activity is high in BMMs. RANKL stimulation enhances the expression of IgSF11. b IgSF11 mediates the phosphorylation of PKM2 through Src family kinases (c-Src, Fyn, and HcK) in a manner dependent on the C-terminal region. This phosphorylation leads to the inhibition of PKM2 activity. In the absence of IgSF11, the inhibition of PKM2 activity barely occurs, keeping PKM2 activity high. c IgSF11-mediated inhibition of PKM2 activity increases osteoclast differentiation. In the absence of IgSF11, osteoclast differentiation is impaired due to a lack of PKM2 inhibition, which can be rescued by the PKM2-specific inhibitor shikonin. Moreover, the PKM2-specific activator TEPP46 inhibits osteoclast differentiation in the presence of IgSF11
