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Article: SLAM-associated protein as a potential negative regulator in Trk signaling

TitleSLAM-associated protein as a potential negative regulator in Trk signaling
Authors
KeywordsSpecies Index: Animalia
Issue Date2005
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 2005, v. 280 n. 50, p. 41744-41752 How to Cite?
AbstractNeurotrophin signaling plays important roles in regulating the survival, differentiation, and maintenance of neurons in the nervous system. Binding of neurotrophins to their cognate receptors Trks induces transactivation and phosphorylation of the receptor at several tyrosine residues. These phosphorylated tyrosine residues then serve as crucial docking sites for adaptor proteins containing a Src homology 2 or phosphotyrosine binding domain, which upon association with the receptor initiates multiple signaling events to mediate the action of neurotrophins. Here we report the identification of a Src homology 2 domain-containing molecule, SLAM-associated protein (SAP), as an interacting protein of TrkB in a yeast two-hybrid screen. SAP was initially identified as an adaptor molecule in SLAM family receptor signaling for regulating interferon-γ secretion. In the current study, we found that SAP interacted with TrkA, TrkB, and TrkC receptors in vitro and in vivo. Binding of SAP required Trk receptor activation and phosphorylation at the tyrosine 674 residue, which is located in the activation loop of the kinase domain. Overexpression of SAP with Trk attenuated tyrosine phosphorylation of the receptors and reduced the binding of SH2B and She to TrkB. Moreover, overexpression of SAP in PC12 cells suppressed the nerve growth factor-dependent activation of extracellular signal-regulated kinases 1/2 and phospholipase Cγ, in addition to inhibiting neurite outgrowth. In summary, our findings demonstrated that SAP may serve as a negative regulator of Trk receptor activation and downstream signaling. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.
Persistent Identifierhttp://hdl.handle.net/10722/145825
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLo, KYen_HK
dc.contributor.authorChin, WHen_HK
dc.contributor.authorNg, YPen_HK
dc.contributor.authorCheng, AWen_HK
dc.contributor.authorCheung, ZHen_HK
dc.contributor.authorIp, NYen_HK
dc.date.accessioned2012-03-23T09:49:51Z-
dc.date.available2012-03-23T09:49:51Z-
dc.date.issued2005en_HK
dc.identifier.citationJournal Of Biological Chemistry, 2005, v. 280 n. 50, p. 41744-41752en_HK
dc.identifier.issn0021-9258en_HK
dc.identifier.urihttp://hdl.handle.net/10722/145825-
dc.description.abstractNeurotrophin signaling plays important roles in regulating the survival, differentiation, and maintenance of neurons in the nervous system. Binding of neurotrophins to their cognate receptors Trks induces transactivation and phosphorylation of the receptor at several tyrosine residues. These phosphorylated tyrosine residues then serve as crucial docking sites for adaptor proteins containing a Src homology 2 or phosphotyrosine binding domain, which upon association with the receptor initiates multiple signaling events to mediate the action of neurotrophins. Here we report the identification of a Src homology 2 domain-containing molecule, SLAM-associated protein (SAP), as an interacting protein of TrkB in a yeast two-hybrid screen. SAP was initially identified as an adaptor molecule in SLAM family receptor signaling for regulating interferon-γ secretion. In the current study, we found that SAP interacted with TrkA, TrkB, and TrkC receptors in vitro and in vivo. Binding of SAP required Trk receptor activation and phosphorylation at the tyrosine 674 residue, which is located in the activation loop of the kinase domain. Overexpression of SAP with Trk attenuated tyrosine phosphorylation of the receptors and reduced the binding of SH2B and She to TrkB. Moreover, overexpression of SAP in PC12 cells suppressed the nerve growth factor-dependent activation of extracellular signal-regulated kinases 1/2 and phospholipase Cγ, in addition to inhibiting neurite outgrowth. In summary, our findings demonstrated that SAP may serve as a negative regulator of Trk receptor activation and downstream signaling. © 2005 by The American Society for Biochemistry and Molecular Biology, Inc.en_HK
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_HK
dc.relation.ispartofJournal of Biological Chemistryen_HK
dc.subjectSpecies Index: Animaliaen_US
dc.subject.meshAmino Acid Sequenceen_HK
dc.subject.meshAnimalsen_HK
dc.subject.meshBlotting, Southernen_HK
dc.subject.meshBlotting, Westernen_HK
dc.subject.meshBrain - metabolismen_HK
dc.subject.meshCell Lineen_HK
dc.subject.meshDNA, Complementary - metabolismen_HK
dc.subject.meshFungal Proteins - metabolismen_HK
dc.subject.meshHumansen_HK
dc.subject.meshImmunohistochemistryen_HK
dc.subject.meshInterferon-gamma - metabolismen_HK
dc.subject.meshIntracellular Signaling Peptides and Proteins - metabolism - physiologyen_HK
dc.subject.meshMiceen_HK
dc.subject.meshMicroscopy, Fluorescenceen_HK
dc.subject.meshModels, Geneticen_HK
dc.subject.meshMolecular Sequence Dataen_HK
dc.subject.meshMutationen_HK
dc.subject.meshNerve Growth Factors - metabolismen_HK
dc.subject.meshNeurons - metabolismen_HK
dc.subject.meshPC12 Cellsen_HK
dc.subject.meshPhosphorylationen_HK
dc.subject.meshProtein Bindingen_HK
dc.subject.meshProtein Structure, Tertiaryen_HK
dc.subject.meshRatsen_HK
dc.subject.meshReceptor, trkA - metabolismen_HK
dc.subject.meshRecombinant Fusion Proteins - chemistryen_HK
dc.subject.meshSignal Transductionen_HK
dc.subject.meshTwo-Hybrid System Techniquesen_HK
dc.subject.meshTyrosine - chemistryen_HK
dc.subject.meshsrc Homology Domainsen_HK
dc.titleSLAM-associated protein as a potential negative regulator in Trk signalingen_HK
dc.typeArticleen_HK
dc.identifier.emailCheung, ZH:zelda@hku.hken_HK
dc.identifier.authorityCheung, ZH=rp01588en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1074/jbc.M506554200en_HK
dc.identifier.pmid16223723-
dc.identifier.scopuseid_2-s2.0-29244481978en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-29244481978&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume280en_HK
dc.identifier.issue50en_HK
dc.identifier.spage41744en_HK
dc.identifier.epage41752en_HK
dc.identifier.eissn1083-351X-
dc.identifier.isiWOS:000233866900076-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridLo, KY=10139289400en_HK
dc.identifier.scopusauthoridChin, WH=10141627600en_HK
dc.identifier.scopusauthoridNg, YP=7202471018en_HK
dc.identifier.scopusauthoridCheng, AW=36788763800en_HK
dc.identifier.scopusauthoridCheung, ZH=6507483375en_HK
dc.identifier.scopusauthoridIp, NY=7005756760en_HK

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