Please use this identifier to cite or link to this item: 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
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
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