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dc.contributor.authorSmith, F. Donelson
dc.contributor.authorLangeberg, Lorene K.
dc.contributor.authorCellurale, Cristina Arrigo
dc.contributor.authorPawson, Tony
dc.contributor.authorMorrison, Deborah K.
dc.contributor.authorDavis, Roger J.
dc.contributor.authorScott, John D.
dc.date2022-08-11T08:08:16.000
dc.date.accessioned2022-08-23T15:48:51Z
dc.date.available2022-08-23T15:48:51Z
dc.date.issued2010-12-01
dc.date.submitted2016-02-29
dc.identifier.citationNat Cell Biol. 2010 Dec;12(12):1242-9. doi: 10.1038/ncb2130. Epub 2010 Nov 21. <a href="http://dx.doi.org/10.1038/ncb2130">Link to article on publisher's site</a>
dc.identifier.issn1465-7392 (Linking)
dc.identifier.doi10.1038/ncb2130
dc.identifier.pmid21102438
dc.identifier.urihttp://hdl.handle.net/20.500.14038/28299
dc.description.abstractMitogen-activated protein kinase (MAPK) cascades propagate a variety of cellular activities. Processive relay of signals through RAF-MEK-ERK modulates cell growth and proliferation. Signalling through this ERK cascade is frequently amplified in cancers, and drugs such as sorafenib (which is prescribed to treat renal and hepatic carcinomas) and PLX4720 (which targets melanomas) inhibit RAF kinases. Natural factors that influence ERK1/2 signalling include the second messenger cyclic AMP. However, the mechanisms underlying this cascade have been difficult to elucidate. We demonstrate that the A-kinase-anchoring protein AKAP-Lbc and the scaffolding protein kinase suppressor of Ras (KSR-1) form the core of a signalling network that efficiently relay signals from RAF, through MEK, and on to ERK1/2. AKAP-Lbc functions as an enhancer of ERK signalling by securing RAF in the vicinity of MEK1 and synchronizing protein kinase A (PKA)-mediated phosphorylation of Ser 838 on KSR-1. This offers mechanistic insight into cAMP-responsive control of ERK signalling events.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=21102438&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3042953/
dc.subjectA Kinase Anchor Proteins
dc.subjectAmino Acid Sequence
dc.subjectAnimals
dc.subjectCell Line
dc.subjectCyclic AMP
dc.subjectCyclic AMP-Dependent Protein Kinases
dc.subjectHumans
dc.subject*MAP Kinase Signaling System
dc.subjectMice
dc.subjectMitogen-Activated Protein Kinase 1
dc.subjectMitogen-Activated Protein Kinase 3
dc.subjectMolecular Sequence Data
dc.subjectProtein Kinases
dc.subjectProto-Oncogene Proteins
dc.subjectSequence Alignment
dc.subjectBiochemistry
dc.subjectCell Biology
dc.subjectCellular and Molecular Physiology
dc.subjectMolecular Biology
dc.titleAKAP-Lbc enhances cyclic AMP control of the ERK1/2 cascade
dc.typeJournal Article
dc.source.journaltitleNature cell biology
dc.source.volume12
dc.source.issue12
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/davis/29
dc.identifier.contextkey8234482
html.description.abstract<p>Mitogen-activated protein kinase (MAPK) cascades propagate a variety of cellular activities. Processive relay of signals through RAF-MEK-ERK modulates cell growth and proliferation. Signalling through this ERK cascade is frequently amplified in cancers, and drugs such as sorafenib (which is prescribed to treat renal and hepatic carcinomas) and PLX4720 (which targets melanomas) inhibit RAF kinases. Natural factors that influence ERK1/2 signalling include the second messenger cyclic AMP. However, the mechanisms underlying this cascade have been difficult to elucidate. We demonstrate that the A-kinase-anchoring protein AKAP-Lbc and the scaffolding protein kinase suppressor of Ras (KSR-1) form the core of a signalling network that efficiently relay signals from RAF, through MEK, and on to ERK1/2. AKAP-Lbc functions as an enhancer of ERK signalling by securing RAF in the vicinity of MEK1 and synchronizing protein kinase A (PKA)-mediated phosphorylation of Ser 838 on KSR-1. This offers mechanistic insight into cAMP-responsive control of ERK signalling events.</p>
dc.identifier.submissionpathdavis/29
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages1242-9


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