Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0023681
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dc.titleTC-PTP dephosphorylates the guanine nucleotide exchange factor C3G (RapGEF1) and negatively regulates differentiation of human neuroblastoma cells
dc.contributor.authorMitra A.
dc.contributor.authorKalayarasan S.
dc.contributor.authorGupta V.
dc.contributor.authorRadha V.
dc.date.accessioned2019-11-11T08:38:23Z
dc.date.available2019-11-11T08:38:23Z
dc.date.issued2011
dc.identifier.citationMitra A., Kalayarasan S., Gupta V., Radha V. (2011). TC-PTP dephosphorylates the guanine nucleotide exchange factor C3G (RapGEF1) and negatively regulates differentiation of human neuroblastoma cells. PLoS ONE 6 (8) : e23681. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0023681
dc.identifier.issn19326203
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/162035
dc.description.abstractThe guanine nucleotide exchange factor, C3G (RapGEF1), functions in multiple signaling pathways involved in cell adhesion, proliferation, apoptosis and actin reorganization. C3G is regulated by tyrosine phosphorylation on Y504, known to be mediated by c-Abl and Src family kinases. In the present study we explored the possibility of cellular phospho-C3G (pC3G) being a substrate of the intracellular T-cell protein tyrosine phosphatase TC-PTP (PTPN2) using the human neuroblastoma cell line, IMR-32. In vivo and in vitro binding assays demonstrated interaction between C3G and TC-PTP. Interaction is mediated through the Crk-binding region of C3G and C-terminal noncatalytic residues of TC-PTP. C3G interacted better with a substrate trap mutant of TC48 and this complex formation was inhibited by vanadate. Endogenous pC3G colocalized with catalytically inactive mutant TC48 in the Golgi. Expression of TC48 abrogated pervanadate and c-Src induced phosphorylation of C3G without affecting total cellular phospho-tyrosine. Insulin-like growth factor treatment of c-Src expressing cells resulted in dephosphorylation of C3G dependent on the activity of endogenous TC48. TC48 expression inhibited forskolin induced tyrosine phosphorylation of C3G and neurite outgrowth in IMR-32 cells. Our results identify a novel Golgi localized substrate of TC48 and delineate a role for TC48 in dephosphorylation of substrates required during differentiation of human neuroblastoma cells. © 2011 Mitra et al.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20191101
dc.subjectforskolin
dc.subjectguanine nucleotide exchange factor
dc.subjectguanine nucleotide exchange factor C3G
dc.subjectnon receptor protein tyrosine phosphatase 2
dc.subjectpervanadate
dc.subjectphosphotyrosine
dc.subjectsomatomedin
dc.subjecttyrosine
dc.subjectunclassified drug
dc.subjectvanadic acid
dc.subjectforskolin
dc.subjectguanine nucleotide exchange factor
dc.subjectmutant protein
dc.subjectnon receptor protein tyrosine phosphatase 2
dc.subjectphosphotyrosine
dc.subjectprotein tyrosine kinase
dc.subjectPTPN2 protein, human
dc.subjectvanadic acid
dc.subjectanimal cell
dc.subjectarticle
dc.subjectbinding assay
dc.subjectcarboxy terminal sequence
dc.subjectcomplex formation
dc.subjectcontrolled study
dc.subjectembryo
dc.subjectenzyme inactivation
dc.subjectenzyme substrate
dc.subjectGolgi complex
dc.subjecthuman
dc.subjecthuman cell
dc.subjectin vitro study
dc.subjectin vivo study
dc.subjectnerve cell differentiation
dc.subjectnerve fiber growth
dc.subjectneuroblastoma
dc.subjectneuroblastoma cell
dc.subjectnonhuman
dc.subjectnucleotide binding site
dc.subjectoncogene src
dc.subjectprotein dephosphorylation
dc.subjectprotein expression
dc.subjectprotein function
dc.subjectprotein localization
dc.subjectprotein phosphorylation
dc.subjectprotein protein interaction
dc.subjectcell differentiation
dc.subjectcell strain HEK293
dc.subjectchemistry
dc.subjectdrug effect
dc.subjectenzymology
dc.subjectmetabolism
dc.subjectneurite
dc.subjectneuroblastoma
dc.subjectpathology
dc.subjectphosphorylation
dc.subjectprotein binding
dc.subjectprotein tertiary structure
dc.subjectprotein transport
dc.subjectstructure activity relation
dc.subjecttumor cell line
dc.subjectCell Differentiation
dc.subjectCell Line, Tumor
dc.subjectForskolin
dc.subjectGolgi Apparatus
dc.subjectGuanine Nucleotide-Releasing Factor 2
dc.subjectHEK293 Cells
dc.subjectHumans
dc.subjectMutant Proteins
dc.subjectNeurites
dc.subjectNeuroblastoma
dc.subjectPhosphorylation
dc.subjectPhosphotyrosine
dc.subjectProtein Binding
dc.subjectProtein Structure, Tertiary
dc.subjectProtein Transport
dc.subjectProtein Tyrosine Phosphatase, Non-Receptor Type 2
dc.subjectsrc-Family Kinases
dc.subjectStructure-Activity Relationship
dc.subjectVanadates
dc.typeArticle
dc.contributor.departmentMECHANOBIOLOGY INSTITUTE
dc.description.doi10.1371/journal.pone.0023681
dc.description.sourcetitlePLoS ONE
dc.description.volume6
dc.description.issue8
dc.description.pagee23681
dc.published.statePublished
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