title: Angiotensin IV upregulates the activity of protein phosphatase 1α in Neura-2A cells.
abstract: 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 using sta ble-isotope labeling by amino acids in cell culture (SILAC), and identified a reduction in the phosphorylation of a major Ser/Thr protein phosphorylase 1 (PP1) upon Ang IV treatment. In addition, spinophilin (spn), a PP1 regulatory protein that plays important functions in the neural system, was expressed at higher levels. Immunoblotting revealed decreased phosphorylation of p70S6 kinase (p70(S6K)) and the major cell cycle modulator retinoblastoma 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.
authors.affiliation: National Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.forename: Peng
authors.initials: P
authors.lastname: Xue
authors.forename: Xiu Lan
authors.initials: XL
authors.lastname: Chen
authors.forename: Zhen Sheng
authors.initials: ZS
authors.lastname: Xie
authors.forename: Fu Quan
authors.initials: FQ
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
mesh_terms: D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology; D010766:Phosphorylation / Q000187:drug effects; D054645:Protein Phosphatase 1 / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D020543:Proteome / Q000378:metabolism; D051381:Rats; D013912:Threonine / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D000099273:Neurabins
chemical_list: D000804:Angiotensin II; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; D054645:Protein Phosphatase 1; D020543:Proteome; D013912:Threonine; D000099273:Neurabins; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-