Ciliary transport regulates PDGF-AA/αα signaling via elevated mammalian target of rapamycin signaling and diminished PP2A activity (Molecular Biology of the Cell 2014, 350-358)

報告日期: 2017/04/25
報告時間: 5:10/6:00
報告學生: 許志祥
講評老師: 王家義
附件下載: 下載[1631-1487731838-1.pdf] 

Ciliary transport regulates PDGF-AA/αα signaling via elevated mammalian target of rapamycin signaling and diminished PP2A activity

Nicole L. Umbergerand Tamara Caspary

Mol Biol Cell. 2015, 350-8

Speaker:Jhih-Siang Syu   Commentator: Prof. Chia-Yih Wang

Date: 2017/04/25

Abstract:

Platelet-derived growth factor(PDGF) is a growth factor which is activated when dimerization. PDGF dimer binds to its receptor, platelet-derived growth factor receptor(PDGFR), which is a receptor tyrosinekinase mainly expressed in the primary cilia. Primary cilium is sensory organellethat displays specific receptors and ion channels. PDGFR in cilia activates downstream pathway, such as protein kinase B(AKT) signaling, to regulate cell division, migration, differentiation, and proliferation. It is known that PDGF-AA fails to phosphorylate AKT in destroying ciliary transport cell and losing of cilia can increase mammalian target of rapamycin (mTOR) signaling. In addition, protein phosphatase 2(PP2A) which is a serine-threonine phosphatase could regulate the activity of AKT and localizes to the centrosome. However, the role of PDGF-induced AKT signaling, mTOR signaling and PP2A in ciliary transport is unclear.

Here they discover that phosphorylation of AKT is increased without PDGF-AA in difference ciliary transport mutants. The anterograde transport mutant reduces the expression level of PDGFR but retrograde transport mutant is not effect. However, the AKT phosphorylation level is not effect both anterograde and retrograde transport mutants in PDGF stimulation. Therefore, they found that PP2A which localizes in ciliary basal body regulates phosphorylation of AKT in ciliary transport mutants and the activity of PP2A is regulated by mTOR1 signaling depend on Ift172.