Quantitative Phosphoproteomics Reveals SLP-76 Dependent Regulation of PAG and Src Family Kinases in T Cells 英文参考文献.docVIP

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Quantitative Phosphoproteomics Reveals SLP-76 Dependent Regulation of PAG and Src Family Kinases in T Cells 英文参考文献.doc

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Quantitative Phosphoproteomics Reveals SLP-76 Dependent Regulation of PAG and Src Family Kinases in T Cells 英文参考文献

QuantitativePhosphoproteomicsRevealsSLP-76 DependentRegulationofPAGandSrcFamilyKinasesin TCells LuluCao1,YiyuanDing1,NorrisHung2,KebingYu1,AnnaRitz3,BenjaminJ.Raphael3, ArthurR.Salomon1,2 * 1DepartmentofChemistry,BrownUniversity,Providence,RhodeIsland,UnitedStatesofAmerica,2DepartmentofMolecularBiology,CellBiology,andBiochemistry, BrownUniversity,Providence,RhodeIsland,UnitedStatesofAmerica,3DepartmentofComputerScience,BrownUniversity,Providence,RhodeIsland,UnitedStatesof America Abstract The SH2-domain-containing leukocyte protein of 76kDa (SLP-76) plays a critical scaffolding role in T cell receptor (TCR) signaling. As an adaptor protein that contains multiple protein-binding domains, SLP-76 interacts with many signaling molecules and links proximal receptor stimulation to downstream effectors. The function of SLP-76 in TCRsignaling has beenwidelystudiedusingtheJurkathumanleukaemicTcelllinethroughproteindisruptionorsite-directedmutagenesis. However,awide-scalecharacterizationofSLP-76-dependantphosphorylationeventsisstilllacking.Quantitativeprofilingof over a hundred tyrosine phosphorylation sites revealed new modes of regulation of phosphorylation of PAG, PI3K, and WASPwhilereconfirmingpreviouslyestablishedregulationofItk,PLCc,andErkphosphorylationbySLP-76.Theabsenceof SLP-76alsoperturbedthephosphorylationofSrcfamilykinases(SFKs)LckandFyn,andsubsequentlyalargenumberof SFK-regulated signaling molecules. Altogether our data suggests unique modes of regulation of positive and negative feedbackpathwaysinTcellsbySLP-76,reconfirmingitscentralroleinthepathway. Citation:CaoL,DingY,HungN,YuK,RitzA,etal.(2012)QuantitativePhosphoproteomicsRevealsSLP-76DependentRegulationofPAGandSrcFamilyKinases inTCells.PLoSONE7(10):e46725.doi:10.1371/journal.pone.0046725 Editor:ArunRishi,WayneStateUniversity,UnitedStatesofAmerica ReceivedApril23,2012;AcceptedSeptember7,2012;PublishedOctober11,2012 Copyright:?2012Caoetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommon