RTE concentration as well, there was little Everolimus RAD001 effect of PTEN activity T observed on the signal, the signal of HRG tot PACT Ttigt to normal levels of PTEN in the model, 40 and 50 nM, which is in line with the experimental data. We conclude S the fact that this hour PIP3 here has no effect on the H Height of the tool Ttigten PACT unrestrained reaching active PTEN. Thus, the concentration of the enzyme AKT is rate-limiting in the activation of Akt by PIP3 in PE04 cells. Note that this effect on the relationship of PIP3 synthesis and initial concentrations of AKT, which differ for different cell lines can k, H depends Depends. A further consequence of the loss of PTEN, and after recd Increase the PIP3 level translocation of PDK1 enzyme PIP3 at the plasma membrane from the cytosol and its activation is induced by PIP3. Our experience in the inhibition of PTEN showed no increase after PACT PIP3 activation induced by PDK1 is, and therefore the analysis of Ausma It reveal the PACT but not the chemical library screening relationship between the degree of activation and the level of PDK1 erh Hte PIP3. A PACT S Saturation, independent Ngig of the H Height of PIP3 PIP3 can activate PDK1 one erh Increase the rate of phosphorylation of AKT, without causing saturation.
The extent PIP3-induced activation of PDK1 from the loss of PTEN can be tested by comparing the effects of inhibition of PDK1 activity different th of PTEN. Our experiments buy Pimecrolimus showed that normal PTEN activity T, it is m Possible, by about 80% of the PACT signal in PE04 cells to HRG sat signal To inhibit ttigt. It is perhaps by inhibiting upstream and downstream PDK1 inhibition with UCN 01, or a combination of RTK inhibitors and UCN-01 In our experiments, in which PTEN activity lost by the action t BPV goes, it is not possible m to inhibit the signal PACT: neither RTK inhibitor, or a combination of RTK inhibitors and UCN-01 has a significant impact on the tot ttigten PACT signal. Thus, our experience has shown that the obtained Hte activity t is obtained due to the PDK1 Hten local concentration of the active PDK1 the effectiveness of inhibition of PDK1 loss of PTEN reduced PE04 in cells. Therefore, rtigen in AP23573 contrast to the inhibition of PI3K in the PTEN upstream, Is the inhibition of PDK1 in the PTEN downstream Rts to the loss of PTEN not restore the inhibitory effect of pertuzumab PE04 cells, and this was D in the activation loop induces PTEN PIP3 way below. 3.6. PTEN-dependent Independent activation of AKT and independent Ngigen As discussed above, we have in silico and in vitro experiments, the Independent dependence of the signal on the PACT PTEN activity t of the receptor cells in PE04 tot ttigten Shown.
However, we have also observed activation of PTEN AKT-dependent Independent signals of unsaturated Ttigten receptor whose inhibition by pertuzumab. The theoretical saturation dependence Dependence on the concentration of the PACT PTEN in HER2 inhibition has been shown that the signal obtained hen to a PAKT decrease in concentration to the S Saturation PTEN PACT. Our experiments best Saturated mutual dependence Dependence of PACT levels of PTEN activity t to its inhibition by pertuzumab in PE04 cells. Based on our modeling showed that the loss of PTEN leads the reinforcing Rkung of the signal to unsaturated Ttigte pHER2 PACT ges Ttigten signal, which confers resistance to inhibition leads HER2. A Similar reciprocal activation h Depends on PTEN AKT was in our in vitro observed E.