Open AccessPathological Signaling via Platelet-Derived Growth Factor Receptor α Involves Chronic Activation of Akt and Suppression of p53
Author(s) -
Hetian Lei,
Gisela Velez,
Andrius Kazlauskas
Publication year - 2011
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.01321-10
Subject(s) - platelet derived growth factor receptor , platelet derived growth factor , protein kinase b , biology , growth factor , cancer research , signal transduction , microbiology and biotechnology , internalization , proliferative vitreoretinopathy , growth factor receptor , receptor , biochemistry , retinal detachment , retinal
In contrast to direct activation of platelet-derived growth factor (PDGF) receptor α (PDGFRα) via PDGF, indirect activation via growth factors outside the PDGF family failed to induce dimerization, internalization, and degradation of PDGFRα. Chronically activated, monomeric PDGFRα induced prolonged activation of Akt and suppressed the level of p53. These events were sufficient to promote both cellular responses (proliferation, survival, and contraction) that are intrinsic to proliferative vitreoretinopathy (PVR) and induce the disease itself. This signature signaling pathway appeared to extend beyond PVR since deregulating PDGFRα in ways that promote solid tumors also resulted in chronic activation of Akt and a decline in the level of p53.