Fig 8.

Model of RANK-mediated osteoclast cytoskeletal organization. Upon RANKL simulation, RANK migrates to c-Src-rich areas of the plasma membrane, where a 5-amino-acid, TRAF-6-interacting motif associates with the tyrosine kinase's SH2 domain in an activated αvβ3-dependent manner. The cytokine receptor and integrin form a complex mediated by c-Src, whose SH3 domain recognizes the β3 cytoplasmic tail. Liganded RANK and αvβ3 collaborate to induce a canonical signaling pathway involving c-Src, Syk Slp-76, Vav3, and Rac, which organize the osteoclast cytoskeleton.