Figure 5.
The PTEN-NHERF1-PHLPP inhibitory network is disabled in glioblastoma. A. Western blot analysis with indicated antibodies of protein extracts (8-10μg) from 9 low-grade glioma and 11 glioblastoma (GBM) samples. The average PHLPP1, NHERF1 and PTEN suppressor levels normalized to IKKβ and P-Akt/Akt levels show statistical significant differences in low-grade versus high-grade tumors. B. The correlation between PHLPP1, NHERF1 and PTEN suppressor levels and P-Akt/Akt levels for individual tumor samples, as sorted by increasing P-Akt/Akt levels (graph), is summarized in the table. Note significant inverse correlation between PHLPP1α levels and Akt phosphorylation in PTEN-negative tumors. C. Model depicting the molecular and functional interrelationships between the triple inhibitory network (gray circle) of PI3K-Akt. The white arrows indicate recruitment of PTEN and PHLPP to the membrane by NHERF1 via PDZ-motif/PDZ-domain interactions and the yellow arrow denotes an alternative lipid membrane association mechanism for PTEN. The Akt-independent suppression of tumor growth is shown with blue blocking lines.