Pathological Signaling via Platelet-Derived Growth Factor Receptor α Involves Chronic Activation of Akt and Suppression of p53
Pathological Signaling via Platelet-Derived Growth Factor Receptor α Involves Chronic Activation of Akt and Suppression of p53
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DOI:
10.1128/mcb.01321-10
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发表时间:
2011-05-01
影响因子:
5.3
通讯作者:
Kazlauskas, Andrius
中科院分区:
文献类型:
--
作者:
Lei, Hetian;Velez, Gisela;Kazlauskas, Andrius
In contrast to direct activation of platelet-derived growth factor (PDGF) receptor alpha (PDGFR alpha) via PDGF,indirect activation via growth factors outside the PDGF family failed to induce dimerization, internalization, and degradation of PDGFR alpha. Chronically activated, monomeric PDGFR alpha 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 PDGFR alpha in ways that promote solid tumors also resulted in chronic activation of Akt and a decline in the level of p53.