SPINOPHILIN(SPN,PPP1R9B or NEURABIN-2)is a multifunctional protein that regulates protein-protein interactions in different cell signaling pathways.SPN is also one of the regulatory subunits of protein phosphatase 1(P...SPINOPHILIN(SPN,PPP1R9B or NEURABIN-2)is a multifunctional protein that regulates protein-protein interactions in different cell signaling pathways.SPN is also one of the regulatory subunits of protein phosphatase 1(PP1),implicated in the dephosphorylation of retinoblastoma protein(pRB)during cell cycle.The SPN gene has been described as a tumor suppressor in different human tumor contexts,in which low levels of SPN are correlated with a higher grade and worse prognosis.In addition,mutations of the SPN protein have been reported in human tumors.Recently,an oncogenic mutation of sPN,A566V,was described,which affects both the SPN-PP1 interaction and the phosphatase activity of the holoenzyme,and promotes p53-dependent tumorigenesis by increasing the cancer stem cell(CsC)pool in breast tumors.Thus,the loss or mutation of SPN could be late events that promotes tumor progression by increasing the CSC pool and,eventually,the malignant behavior of the tumor.展开更多
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 rema...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.展开更多
基金This work was supported by Ministerio de Ciencia,Innovacion y Universidades(MCIU),Plan Estatal de I+D+I 2018,Spain,Agencia Estatal de Investigacion(AEl),Spain,and Regional Development European Funds(FEDER),European Union(No.RTI2018-097455-B-I00 and RED2018-102723)CIBER of Cancer,Spain(No.CB16/12/00275)+2 种基金Consejeria de Salud of the Junta de Andalucia,Spain(No.Pl-0397-2017)Consejeria of Economia,Conocimiento,Empresas y Universidad of the Junta de Andalucia,Spain(No.P18-RT-2501)Fundacion AECC,Spain and Fundacion Eugenio Rodriguez Pascual,Spain.EMV-S was funded by a postdoctoral contract from Consejeria of Transformacion Economica,Industria,Conocimiento,y Universidades of the JuntadeAndalucia,Spain(No.CTEICU/PAIDI2020).
文摘SPINOPHILIN(SPN,PPP1R9B or NEURABIN-2)is a multifunctional protein that regulates protein-protein interactions in different cell signaling pathways.SPN is also one of the regulatory subunits of protein phosphatase 1(PP1),implicated in the dephosphorylation of retinoblastoma protein(pRB)during cell cycle.The SPN gene has been described as a tumor suppressor in different human tumor contexts,in which low levels of SPN are correlated with a higher grade and worse prognosis.In addition,mutations of the SPN protein have been reported in human tumors.Recently,an oncogenic mutation of sPN,A566V,was described,which affects both the SPN-PP1 interaction and the phosphatase activity of the holoenzyme,and promotes p53-dependent tumorigenesis by increasing the cancer stem cell(CsC)pool in breast tumors.Thus,the loss or mutation of SPN could be late events that promotes tumor progression by increasing the CSC pool and,eventually,the malignant behavior of the tumor.
基金the Knowledge Innovation Project of the Chinese Academy of Sciences(KSCX1-YW-02)the National Natural Science Foundation of China(Grant No.30801416).
文摘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.
