Fig. 5.
Negative regulation of PTEN membrane localization through binding sites sensitive to PIP3. a Three diffusion states of DdPTEN, DdPTENG129E and HsPTEN molecules were detected on the low and high PIP3 membranes. The values were normalized to the total number of DdPTEN molecules on the low PIP3 membranes. Error bars: 95% confidence intervals. P = 0.000, 0.002, and 0.000 (low PIP3 vs. high PIP3 for DdPTEN, DdPTENG129E, and HsPTEN) and 0.000 and 0.000 (DdPTEN vs. DdPTENG129E and DdPTEN vs. HsPTEN under the low PIP3 conditions). b Stably (orange) and transiently (blue) binding states of membrane-bound molecules displayed in a time series after the onset of membrane binding. The lines represent the fitting to the solutions of the simultaneous differential equations in equation (6). c State transitions and membrane-dissociation kinetics. Numbers without parenthesis represent rate constants (sec−1). Numbers in parenthesis represent probabilities of adopting the respective state at the moment of membrane association. d Three binding states of DdPTEN molecules undergoing a transient response to uniform cAMP stimulation in pi3k1-5-null cells (n = 3342 molecules, 16 cells). The values were normalized to the total number of DdPTEN molecules before the stimulation. Error bars: 95% confidence intervals. P = 0.004, 0.000, 0.000 and 0.000 (before stimulation vs. 0–5 s, 5–10 s, 10–15 s and 15–20 s after stimulation). P values were obtained by likelihood-ratio test. e A model for negative regulation of PTEN membrane localization. It is assumed that a specific binding site (orange circle) acts as the stabilizer that associates with PTEN in the stably bound state and that this binding site is inhibited by PIP3 via PTEN-dependent and –independent mechanisms as well as by cAMP signaling