The peptide angiotensin IV(Ang IV)is a derivative of angiotensin II.While insulin regulated amino peptidase(IRAP)has been proposed as a potential receptor for Ang IV,the signalling pathways of Ang IV through IRAP remain elusive.We applied high-resolution mass spectrometry to perform a systemic quantitative phosphoproteome of Neura-2A(N2A)cells treated with and without Ang IV us-ing sta ble-isotope labeling by amino acids in cell culture(SILAC),and identifi ed a reduction in the phosphorylation of a major Ser/Thr protein phosphorylase 1(PP1)upon Ang IV treatment.In addition,spinophilin(spn),a PP1 reg-ulatory protein that plays important functions in the neural system,was expressed at higher levels.Immunoblotting revealed decreased phosphorylation of p70S6 kinase(p70S6K)and the major cell cycle modulator retinoblas-toma protein(pRB).These changes are consistent with an observed decrease in cell proliferation.Taken together,our study suggests that Ang IV functions via regulating the activity of PP1.
Dan WangPeng XueXiu Lan ChenZhen Sheng XieFu Quan YangLi ZhengTao Xu
