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https://doi.org/10.1371/journal.pone.0023681
Title: | TC-PTP dephosphorylates the guanine nucleotide exchange factor C3G (RapGEF1) and negatively regulates differentiation of human neuroblastoma cells | Authors: | Mitra A. Kalayarasan S. Gupta V. Radha V. |
Keywords: | forskolin guanine nucleotide exchange factor guanine nucleotide exchange factor C3G non receptor protein tyrosine phosphatase 2 pervanadate phosphotyrosine somatomedin tyrosine unclassified drug vanadic acid forskolin guanine nucleotide exchange factor mutant protein non receptor protein tyrosine phosphatase 2 phosphotyrosine protein tyrosine kinase PTPN2 protein, human vanadic acid animal cell article binding assay carboxy terminal sequence complex formation controlled study embryo enzyme inactivation enzyme substrate Golgi complex human human cell in vitro study in vivo study nerve cell differentiation nerve fiber growth neuroblastoma neuroblastoma cell nonhuman nucleotide binding site oncogene src protein dephosphorylation protein expression protein function protein localization protein phosphorylation protein protein interaction cell differentiation cell strain HEK293 chemistry drug effect enzymology metabolism neurite neuroblastoma pathology phosphorylation protein binding protein tertiary structure protein transport structure activity relation tumor cell line Cell Differentiation Cell Line, Tumor Forskolin Golgi Apparatus Guanine Nucleotide-Releasing Factor 2 HEK293 Cells Humans Mutant Proteins Neurites Neuroblastoma Phosphorylation Phosphotyrosine Protein Binding Protein Structure, Tertiary Protein Transport Protein Tyrosine Phosphatase, Non-Receptor Type 2 src-Family Kinases Structure-Activity Relationship Vanadates |
Issue Date: | 2011 | Citation: | Mitra 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 | Rights: | Attribution 4.0 International | Abstract: | The 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. | Source Title: | PLoS ONE | URI: | https://scholarbank.nus.edu.sg/handle/10635/162035 | ISSN: | 19326203 | DOI: | 10.1371/journal.pone.0023681 | Rights: | Attribution 4.0 International |
Appears in Collections: | Elements Staff Publications |
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