Drosophila Heat Shock Response Requires the JNK Pathway and Phosphorylation of Mixed Lineage Kinase at a Conserved Serine-Proline Motif 英文参考文献.docVIP

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Drosophila Heat Shock Response Requires the JNK Pathway and Phosphorylation of Mixed Lineage Kinase at a Conserved Serine-Proline Motif 英文参考文献.doc

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Drosophila Heat Shock Response Requires the JNK Pathway and Phosphorylation of Mixed Lineage Kinase at a Conserved Serine-Proline Motif 英文参考文献

DrosophilaHeatShockResponseRequirestheJNK PathwayandPhosphorylationofMixedLineageKinase ataConservedSerine-ProlineMotif RebeccaL.Gonda1,RebeccaA.Garlena2,BethStronach2* 1DepartmentofBiologicalSciences,UniversityofPittsburgh,Pittsburgh,Pennsylvania,UnitedStatesofAmerica,2DepartmentofMicrobiologyandMolecularGenetics, UniversityofPittsburghSchoolofMedicine,Pittsburgh,Pennsylvania,UnitedStatesofAmerica Abstract Definingcontextspecificrequirementsforproteinsandpathwaysisamajorchallengeinthestudyofsignaltransduction. Forexample,thestress-activatedproteinkinase(SAPK)pathwaysarecomprisedoffamiliesofcloselyrelatedtransducers that are activated in a variety of tissues and contexts during development and organismal homeostasis. Consequently, redundantandpleiotropiceffectshavehamperedacompleteunderstandingoftheindividualcontributionsoftransducers in distinct contexts. Here, we report on the function of a context-specific regulatory phosphorylation site, PXSP, in the Drosophilamixedlineagekinaseprotein,Slpr,amitogen-activatedproteinkinasekinasekinase(MAP3K)intheJunKinase (JNK)pathway.Geneticanalysisofthefunctionofnon-phosphorylatable(PXAP)andphosphomimeticmutant(PXEP)Slpr transgenesinseveraldistinctcontextsrevealedminimaleffectsinJNK-dependenttissueclosureprocessesbutdifferential requirementsinheatstressresponse.Inparticular,PXAPexpressionresultedinsensitivityofadultstosustainedheatshock, likep38andJNKpathwaymutants.Incontrast,PXEPoverexpressionconferredsomeresistance.Indeed,phosphorylationof thePXSPmotifisenrichedunderheatshockconditionsandrequiresinpart,thep38kinasesfortheenrichment.Thesedata suggestthatcoordinationofsignalingbetweenp38andSlprservestomaintainJNKsignalingduringheatstress.Insum,we demonstrateanovelroleforJNKsignalingintheheatshockresponseinfliesandidentifyaposttranslationalmodification on Slpr, at a conserved site among MAP3K mixed lineage kinase family members, which bolsters stress resistance with negligibleeffectsonJNK-dependentdevelopmentalprocesses. Citat