PTEN Hopping on the Cell Membrane Is Regulated via a Positively-Charged C2 Domain
Figure 7
A “search-and-stabilization” model describes the role of the cα2 helix in the PTEN-membrane interaction.
PTEN mainly adopts three states on the membrane: a stabilized state (S1), two cα2-related states (S2, S3) plus a hopping state. The cα2 helix is involved in suppressing the membrane dissociation of PTEN by directly regulating the latter two states. When the state changes from S2 or S3 to S1, the membrane interaction becomes stabilized and the substrate PI(3,4,5)P3 is more accessible. In the S2 and S3 states, PTEN exhibits membrane dissociation at a faster rate than in the S1 state. Of the dissociating molecules, 8% rebind to the membrane after hopping, which offers a chance for PTEN to search for the substrate again.