R183W mutant of PPP2R1A the gene encoding the PP2A Aalpha scaffolding subunit failed to suppress tumor growth in vivo through activation of the MAPK pathway in RAS-mutant transformed cells. Cells expressing R183W were less sensitive to MEK inhibitors. Results demonstrate that the R183W mutation in PPP2R1A potentiates oncogenic signaling and reduces drug sensitivity of RAS-mutant cells to MEK inhibitors.
In addition 6 other cancer-associated genes (BRAF NRAS HRAS ERK1 ERK2 and PTEN) were also analyzed. In total four somatic mutations were identified in three out of 101 ovarian endometriotic lesions (4% 4/101) including a KRAS p.G12V a PPP2R1A p.S256F and two ARID1A nonsense mutations (p.Q403* and p.G1926*); while no mutations were identified in the remaining 7 genes (BRAF NRAS HRAS ERK1 ERK2 PTEN and PIK3CA)
RAB9 competes with the catalytic subunit PPP2CA in binding to PPP2R1A. This competitive association has an important role in controlling the PP2A catalytic activity.
PPP2R1A mutations occur in a subset of gastrointestinal stromal tumors and are associated with a high malignant potential that leads to decreased disease-free survival and overall survival
Total PP2A activity and PPP2R1A-associated PP2Ac activity were significantly increased in cells overexpressing PPP2R1A-WT. In addition overexpression of PPP2R1A-WT increased cell proliferation in vitro and tumor growth in vivo
Our results suggest that IH-induced ROS generation increases PP2A activation and subsequently downregulates ERK1/2 activation which results in inhibition of PC12 cell proliferation through G0/G1 phase arrest and NGF-induced neuronal differentiation.
We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.