Figure 1.

Integrin inside-out signaling. Shown is a simplified representation of the integrin inside-out process, which regulates integrin activation (i.e., integrin conformation switch from bent-closed or extended-closed to extended-open conformation). Cell signaling initiated by receptors such as chemokine receptors, T cell receptor (TCR), Toll-like receptors (TLR), and selectins, among others, trigger the switch from Rap1-GDP to Rap1-GTP which, either dependently of RIAM or not, activate Talin and enable its binding to the β-cytoplasmic tail of the integrin. Finally, Kindlin binds to the β-cytoplasmic tail of the integrin, and together with talin induces the separation of the cytoplasmic tails, and triggers the activation of the ligand-binding domain. The extended-open conformation of the integrin remains stable with Talin and Kindlin bound.