Ontology type: schema:ScholarlyArticle Open Access: True
2018-06-28
AUTHORSMinwoo Baek, Mihwa Kim, Jae Sung Lim, Liza D. Morales, Joselin Hernandez, Srinivas Mummidi, Sarah Williams-Blangero, Ik-Soon Jang, Andrew T. Tsin, Dae Joon Kim
ABSTRACTUVB exposure can contribute to the development of skin cancer by modulating protein tyrosine kinase (PTK) signaling. It has been suggested that UVB radiation increases the ligand-dependent activation of PTKs and induces PTP inactivation. Our recent studies have shown that T-cell protein tyrosine phosphatase (TC-PTP) attenuates skin carcinogenesis induced by chemical regimens, which indicates its critical role in the prevention of skin cancer. In the current work, we report that TC-PTP increases keratinocyte susceptibility to UVB-induced apoptosis via the downregulation of Flk-1/JNK signaling. We showed that loss of TC-PTP led to resistance to UVB-induced apoptosis in vivo epidermis. We established immortalized primary keratinocytes (IPKs) from epidermal-specific TC-PTP-deficient (K14Cre.Ptpn2fl/fl) mice. Immortalized TC-PTP-deficient keratinocytes (TC-PTP/KO IPKs) showed increased cell survival against UVB-induced apoptosis which was concomitant with a UVB-mediated increase in Flk-1 phosphorylation, especially on tyrosine residue 1173. Inhibition of Flk-1 by either its specific inhibitors or siRNA in TC-PTP/KO IPKs reversed this effect and significantly increased cell death after UVB irradiation in comparison with untreated TC-PTP/KO IPKs. Immunoprecipitation analysis using the TC-PTP substrate-trapping mutant TCPTP-D182A indicated that TC-PTP directly interacts with Flk-1 to dephosphorylate it and their interaction was stimulated by UVB. Following UVB-mediated Flk-1 activation, the level of JNK phosphorylation was also significantly increased in TC-PTP/KO IPKs compared to control IPKs. Similar to our results with Flk-1, treatment of TC-PTP/KO IPKs with the JNK inhibitor SP600125 significantly increased apoptosis after UVB irradiation, confirming that the effect of TC-PTP on UVB-mediated apoptosis is regulated by Flk-1/JNK signaling. Western blot analysis showed that both phosphorylated Flk-1 and phosphorylated JNK were significantly increased in the epidermis of TC-PTP-deficient mice compared to control mice following UVB. Our results suggest that TC-PTP plays a protective role against UVB-induced keratinocyte cell damage by promoting apoptosis via negative regulation of Flk-1/JNK survival signaling. More... »
PAGES730
http://scigraph.springernature.com/pub.10.1038/s41419-018-0781-9
DOIhttp://dx.doi.org/10.1038/s41419-018-0781-9
DIMENSIONShttps://app.dimensions.ai/details/publication/pub.1105164716
PUBMEDhttps://www.ncbi.nlm.nih.gov/pubmed/29955047
JSON-LD is the canonical representation for SciGraph data.
TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT
[
{
"@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json",
"about": [
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/06",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Biological Sciences",
"type": "DefinedTerm"
},
{
"id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/0601",
"inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/",
"name": "Biochemistry and Cell Biology",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Animals",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Apoptosis",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Cell Survival",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Cells, Cultured",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Epidermal Cells",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Epidermis",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Gene Deletion",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Keratinocytes",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "MAP Kinase Signaling System",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Mice",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Mice, Knockout",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Organ Specificity",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Phosphorylation",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Protein Tyrosine Phosphatase, Non-Receptor Type 2",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Tyrosine",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Ultraviolet Rays",
"type": "DefinedTerm"
},
{
"inDefinedTermSet": "https://www.nlm.nih.gov/mesh/",
"name": "Vascular Endothelial Growth Factor Receptor-2",
"type": "DefinedTerm"
}
],
"author": [
{
"affiliation": {
"alternateName": "Present Address: College of Pharmacy, University of Minnesota, Duluth, MN USA",
"id": "http://www.grid.ac/institutes/grid.17635.36",
"name": [
"Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA",
"Present Address: College of Pharmacy, University of Minnesota, Duluth, MN USA"
],
"type": "Organization"
},
"familyName": "Baek",
"givenName": "Minwoo",
"id": "sg:person.07540120723.58",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07540120723.58"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA",
"id": "http://www.grid.ac/institutes/grid.449717.8",
"name": [
"Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA"
],
"type": "Organization"
},
"familyName": "Kim",
"givenName": "Mihwa",
"id": "sg:person.01271275015.88",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01271275015.88"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA",
"id": "http://www.grid.ac/institutes/grid.449717.8",
"name": [
"Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA"
],
"type": "Organization"
},
"familyName": "Lim",
"givenName": "Jae Sung",
"id": "sg:person.01233647240.02",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01233647240.02"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA",
"id": "http://www.grid.ac/institutes/grid.449717.8",
"name": [
"Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA",
"South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA"
],
"type": "Organization"
},
"familyName": "Morales",
"givenName": "Liza D.",
"id": "sg:person.01364104577.09",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01364104577.09"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA",
"id": "http://www.grid.ac/institutes/grid.449717.8",
"name": [
"Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA",
"South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA"
],
"type": "Organization"
},
"familyName": "Hernandez",
"givenName": "Joselin",
"id": "sg:person.01346773420.78",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01346773420.78"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA",
"id": "http://www.grid.ac/institutes/grid.449717.8",
"name": [
"Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA",
"South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA"
],
"type": "Organization"
},
"familyName": "Mummidi",
"givenName": "Srinivas",
"id": "sg:person.0703073716.05",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.0703073716.05"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA",
"id": "http://www.grid.ac/institutes/grid.449717.8",
"name": [
"Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA",
"South Texas Diabetes and Obesity Institute, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA"
],
"type": "Organization"
},
"familyName": "Williams-Blangero",
"givenName": "Sarah",
"id": "sg:person.01147407423.80",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01147407423.80"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon, 305-333 Republic of Korea",
"id": "http://www.grid.ac/institutes/grid.410885.0",
"name": [
"Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon, 305-333 Republic of Korea"
],
"type": "Organization"
},
"familyName": "Jang",
"givenName": "Ik-Soon",
"id": "sg:person.01317070447.13",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01317070447.13"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA",
"id": "http://www.grid.ac/institutes/grid.449717.8",
"name": [
"Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA"
],
"type": "Organization"
},
"familyName": "Tsin",
"givenName": "Andrew T.",
"id": "sg:person.01150550701.84",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01150550701.84"
],
"type": "Person"
},
{
"affiliation": {
"alternateName": "Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA",
"id": "http://www.grid.ac/institutes/grid.449717.8",
"name": [
"Department of Biomedical Sciences, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA",
"Department of Human Genetics, School of Medicine, University of Texas Rio Grande Valley, Edinburg, TX USA"
],
"type": "Organization"
},
"familyName": "Kim",
"givenName": "Dae Joon",
"id": "sg:person.01103556602.33",
"sameAs": [
"https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01103556602.33"
],
"type": "Person"
}
],
"citation": [
{
"id": "sg:pub.10.2119/2006-00024.man",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1068964929",
"https://doi.org/10.2119/2006-00024.man"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.cr.7290262",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1047617709",
"https://doi.org/10.1038/sj.cr.7290262"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nrm2039",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1021713482",
"https://doi.org/10.1038/nrm2039"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/srep45077",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1084132925",
"https://doi.org/10.1038/srep45077"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.onc.1205263",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1044698881",
"https://doi.org/10.1038/sj.onc.1205263"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nprot.2008.50",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1032918181",
"https://doi.org/10.1038/nprot.2008.50"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/nrm.2016.87",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1043242363",
"https://doi.org/10.1038/nrm.2016.87"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1007/s12079-016-0352-8",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1034190207",
"https://doi.org/10.1007/s12079-016-0352-8"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.onc.1211029",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1020671631",
"https://doi.org/10.1038/sj.onc.1211029"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/sj.onc.1203483",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1005181530",
"https://doi.org/10.1038/sj.onc.1203483"
],
"type": "CreativeWork"
},
{
"id": "sg:pub.10.1038/cddis.2017.4",
"sameAs": [
"https://app.dimensions.ai/details/publication/pub.1083405344",
"https://doi.org/10.1038/cddis.2017.4"
],
"type": "CreativeWork"
}
],
"datePublished": "2018-06-28",
"datePublishedReg": "2018-06-28",
"description": "UVB exposure can contribute to the development of skin cancer by modulating protein tyrosine kinase (PTK) signaling. It has been suggested that UVB radiation increases the ligand-dependent activation of PTKs and induces PTP inactivation. Our recent studies have shown that T-cell protein tyrosine phosphatase (TC-PTP) attenuates skin carcinogenesis induced by chemical regimens, which indicates its critical role in the prevention of skin cancer. In the current work, we report that TC-PTP increases keratinocyte susceptibility to UVB-induced apoptosis via the downregulation of Flk-1/JNK signaling. We showed that loss of TC-PTP led to resistance to UVB-induced apoptosis in vivo epidermis. We established immortalized primary keratinocytes (IPKs) from epidermal-specific TC-PTP-deficient (K14Cre.Ptpn2fl/fl) mice. Immortalized TC-PTP-deficient keratinocytes (TC-PTP/KO IPKs) showed increased cell survival against UVB-induced apoptosis which was concomitant with a UVB-mediated increase in Flk-1 phosphorylation, especially on tyrosine residue 1173. Inhibition of Flk-1 by either its specific inhibitors or siRNA in TC-PTP/KO IPKs reversed this effect and significantly increased cell death after UVB irradiation in comparison with untreated TC-PTP/KO IPKs. Immunoprecipitation analysis using the TC-PTP substrate-trapping mutant TCPTP-D182A indicated that TC-PTP directly interacts with Flk-1 to dephosphorylate it and their interaction was stimulated by UVB. Following UVB-mediated Flk-1 activation, the level of JNK phosphorylation was also significantly increased in TC-PTP/KO IPKs compared to control IPKs. Similar to our results with Flk-1, treatment of TC-PTP/KO IPKs with the JNK inhibitor SP600125 significantly increased apoptosis after UVB irradiation, confirming that the effect of TC-PTP on UVB-mediated apoptosis is regulated by Flk-1/JNK signaling. Western blot analysis showed that both phosphorylated Flk-1 and phosphorylated JNK were significantly increased in the epidermis of TC-PTP-deficient mice compared to control mice following UVB. Our results suggest that TC-PTP plays a protective role against UVB-induced keratinocyte cell damage by promoting apoptosis via negative regulation of Flk-1/JNK survival signaling.",
"genre": "article",
"id": "sg:pub.10.1038/s41419-018-0781-9",
"inLanguage": "en",
"isAccessibleForFree": true,
"isFundedItemOf": [
{
"id": "sg:grant.5053600",
"type": "MonetaryGrant"
},
{
"id": "sg:grant.2504295",
"type": "MonetaryGrant"
}
],
"isPartOf": [
{
"id": "sg:journal.1042939",
"issn": [
"2041-4889"
],
"name": "Cell Death & Disease",
"publisher": "Springer Nature",
"type": "Periodical"
},
{
"issueNumber": "7",
"type": "PublicationIssue"
},
{
"type": "PublicationVolume",
"volumeNumber": "9"
}
],
"keywords": [
"protein tyrosine kinases",
"TC-PTP",
"Flk-1",
"JNK signaling",
"skin cancer",
"UVB irradiation",
"cell protein tyrosine phosphatase",
"cell survival",
"Epidermal-specific deletion",
"protein tyrosine phosphatase",
"ligand-dependent activation",
"Western blot analysis",
"UVB-induced apoptosis",
"JNK inhibitor SP600125",
"skin carcinogenesis",
"protective role",
"PTP inactivation",
"UVB exposure",
"tyrosine phosphatase",
"vivo epidermis",
"cell damage",
"negative regulation",
"immunoprecipitation analysis",
"tyrosine kinase",
"primary keratinocytes",
"phosphorylated JNK",
"mice",
"UVB",
"JNK phosphorylation",
"inhibitor SP600125",
"cell death",
"keratinocyte susceptibility",
"survival",
"specific inhibitor",
"UVB radiation",
"apoptosis",
"blot analysis",
"cancer",
"signaling",
"Recent studies",
"keratinocytes",
"phosphorylation",
"critical role",
"chemical regimens",
"activation",
"regulation",
"epidermis",
"regimens",
"prevention",
"carcinogenesis",
"TCPTP",
"death",
"downregulation",
"kinase",
"siRNA",
"treatment",
"SP600125",
"JNK",
"inhibitors",
"inhibition",
"role",
"exposure",
"deletion",
"phosphatase",
"effect",
"inactivation",
"susceptibility",
"damage",
"levels",
"study",
"irradiation",
"increase",
"loss",
"resistance",
"analysis",
"results",
"interaction",
"development",
"current work",
"comparison",
"radiation",
"work",
"Flk-1/JNK signaling",
"IPKs",
"Immortalized TC-PTP-deficient keratinocytes",
"TC-PTP-deficient keratinocytes",
"UVB-mediated increase",
"Flk-1 phosphorylation",
"tyrosine residue 1173",
"residue 1173",
"TC-PTP/KO IPKs",
"KO IPKs",
"untreated TC-PTP/KO IPKs",
"TC-PTP substrate-trapping mutant TCPTP",
"substrate-trapping mutant TCPTP",
"mutant TCPTP",
"D182A",
"Flk-1 activation",
"TC-PTP-deficient mice",
"keratinocyte cell damage",
"Flk-1/JNK survival",
"JNK survival",
"TC-PTP promotes UVB-induced epidermal cell survival",
"promotes UVB-induced epidermal cell survival",
"UVB-induced epidermal cell survival",
"epidermal cell survival"
],
"name": "Epidermal-specific deletion of TC-PTP promotes UVB-induced epidermal cell survival through the regulation of Flk-1/JNK signaling",
"pagination": "730",
"productId": [
{
"name": "dimensions_id",
"type": "PropertyValue",
"value": [
"pub.1105164716"
]
},
{
"name": "doi",
"type": "PropertyValue",
"value": [
"10.1038/s41419-018-0781-9"
]
},
{
"name": "pubmed_id",
"type": "PropertyValue",
"value": [
"29955047"
]
}
],
"sameAs": [
"https://doi.org/10.1038/s41419-018-0781-9",
"https://app.dimensions.ai/details/publication/pub.1105164716"
],
"sdDataset": "articles",
"sdDatePublished": "2022-01-01T18:48",
"sdLicense": "https://scigraph.springernature.com/explorer/license/",
"sdPublisher": {
"name": "Springer Nature - SN SciGraph project",
"type": "Organization"
},
"sdSource": "s3://com-springernature-scigraph/baseset/20220101/entities/gbq_results/article/article_773.jsonl",
"type": "ScholarlyArticle",
"url": "https://doi.org/10.1038/s41419-018-0781-9"
}
]Download the RDF metadata as: json-ld nt turtle xml License info
JSON-LD is a popular format for linked data which is fully compatible with JSON.
curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41419-018-0781-9'
N-Triples is a line-based linked data format ideal for batch operations.
curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41419-018-0781-9'
Turtle is a human-readable linked data format.
curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41419-018-0781-9'
RDF/XML is a standard XML format for linked data.
curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41419-018-0781-9'
This table displays all metadata directly associated to this object as RDF triples.
357 TRIPLES
22 PREDICATES
160 URIs
141 LITERALS
24 BLANK NODES