Lck regulation by Aurora-A. A: Direct regulation of Lck by Aurora-A. (1) Aurora-A regulates the vesicular traffic of Lck through the microtubule network. (2) Possible phosphorylation of Lck by Aurora-A in an unknown residue promotes autophosphorylation in Y394 and proper translocation to the IS region. B: Indirect regulation of Lck by Aurora-A. In resting T cells, the PAG/Cbp complex bound to Csk promotes the binding of Csk with Lck, inhibiting it by the phosphorylation of Y505 residue. The phosphatase CD45 is located at the IS region. During T cell activation, (1) the PAG/Cbp complex promotes the release of Lck by Csk, activating it. Proper Aurora-A localization at the IS could be regulating this mechanism through the phosphorylation of the PAG/Cbp complex or Csk directly. (2) After TCR triggering, the phosphatase CD45 is excluded from the IS. GA, Golgi apparatus; TCR, T cell receptor.