Table 1.
PP2A Interaction | Upstream | Downstream | Physiological effect | Disease | Ref. | |
---|---|---|---|---|---|---|
Inhibitory | ||||||
CIP2A | Directly inhibits PP2A | ↑EGFR |
↓ERK ↑MMP1 and MMP9 |
ECM degradation | COPD, Lung Cancer | [28, 82] |
↓ELK-1 ↑AKT |
Cell survival | Lung Cancer | [94, 95, 98, 104, 106] | |||
↑c-MYC | Proliferation, self-renewal and oncogenic transformation | Lung Cancer | [70, 95, 99, 103] | |||
↑MKK4, JNK, ATF2, c-jun | Proliferation | Lung Cancer | [36] | |||
SET | Directly inhibits PP2A |
↑AKT, cyclin D1, MMP9 ↓P27 |
Proliferation, ECM degradation and invasion | Lung Cancer | [34, 35] | |
↑PCDH7 |
↑ERK, cyclin D1, MMP9 ↓P27 |
Proliferation, ECM degradation and invasion | Lung Cancer | [34, 35, 83] | ||
↑c-MYC ↓NRDG1, RIPK1 |
Invasion, oncogenic transformation and metastasis | Lung Cancer | [34, 113] | |||
PME-1 | Stablises inactive PP2A | ↑ERK, AKT | Proliferation | Lung Cancer | [81] | |
MID1 | Degrades PP2A-C | ↑TRAIL | Fibrosis, collagen deposition, cell survival and proliferation | Asthma, Pulmonary fibrosis, Lung cancer | [116, 117] | |
Beneficial | ||||||
Calpains | PP2A inactivates calpains | ↓μ - and m-calpains | Suppression of invasion and migration, and wound healing | Lung Cancer | [123, 124] | |
Rho B | Rho B binds to PP2A-B55 to increase active PP2A | ↑RASSF1A |
↓AKT-1 ↑GEF-H1 |
suppression of invasion and migration | Lung Cancer | [125, 126] [128] |
TTP | PP2A activates TTP | ↓P38- MAPK, MK2 |
↓IL-6, IL-8 ↓LATS2, cyclin B1 |
Suppression of inflammation and proliferation. | COPD, Asthma, Lung cancer | [29–31] |