| http://purl.uniprot.org/citations/17548351 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/17548351 | http://www.w3.org/2000/01/rdf-schema#comment | "UV radiation induces various cellular responses by regulating the activity of many UV-responsive enzymes, including MAPKs. The betagamma subunit of the heterotrimeric GTP-binding protein (Gbetagamma) was found to mediate UV-induced p38 activation via epidermal growth factor receptor (EGFR). However, it is not known how Gbetagamma mediates the UVB-induced activation of EGFR, and thus we undertook this study to elucidate the mechanism. Treatment of HaCaT-immortalized human keratinocytes with conditioned medium obtained from UVB-irradiated cells induced the phosphorylations of EGFR, p38, and ERK but not that of JNK. Blockade of heparin-binding EGF-like growth factor (HB-EGF) by neutralizing antibody or CRM197 toxin inhibited the UVB-induced activations of EGFR, p38, and ERK in normal human epidermal keratinocytes and in HaCaT cells. Treatment with HB-EGF also activated EGFR, p38, and ERK. UVB radiation stimulated the processing of pro-HB-EGF and increased the secretion of soluble HB-EGF in medium, which was quantified by immunoblotting and protein staining. In addition, treatment with CRM179 toxin blocked UV-induced apoptosis, but HB-EGF augmented this apoptosis. Moreover, UVB-induced apoptosis was reduced by inhibiting EGFR or p38. The overexpression of Gbeta(1)gamma(2) increased EGFR-activating activity and soluble HB-EGF content in conditioned medium, but the sequestration of Gbetagamma by the carboxyl terminus of G protein-coupled receptor kinase 2 (GRK2ct) produced the opposite effect. The activation of Src increased UVB-induced, Gbetagamma-mediated HB-EGF secretion, but the inhibition of Src blocked that. Overexpression of Gbetagamma increased UVB-induced apoptosis, and the overexpression of GRK2ct decreased this apoptosis. We conclude that Gbetagamma mediates UVB-induced human keratinocyte apoptosis by augmenting the ectodomain shedding of HB-EGF, which sequentially activates EGFR and p38."xsd:string |
| http://purl.uniprot.org/citations/17548351 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m702343200"xsd:string |
| http://purl.uniprot.org/citations/17548351 | http://purl.uniprot.org/core/author | "Kim Y."xsd:string |
| http://purl.uniprot.org/citations/17548351 | http://purl.uniprot.org/core/author | "Kim S.Y."xsd:string |
| http://purl.uniprot.org/citations/17548351 | http://purl.uniprot.org/core/author | "Seo M."xsd:string |
| http://purl.uniprot.org/citations/17548351 | http://purl.uniprot.org/core/author | "Lee M.J."xsd:string |
| http://purl.uniprot.org/citations/17548351 | http://purl.uniprot.org/core/author | "Lee Y.I."xsd:string |
| http://purl.uniprot.org/citations/17548351 | http://purl.uniprot.org/core/author | "Lee E.S."xsd:string |
| http://purl.uniprot.org/citations/17548351 | http://purl.uniprot.org/core/author | "Heo J.H."xsd:string |
| http://purl.uniprot.org/citations/17548351 | http://purl.uniprot.org/core/author | "Juhnn Y.S."xsd:string |
| http://purl.uniprot.org/citations/17548351 | http://purl.uniprot.org/core/date | "2007"xsd:gYear |
| http://purl.uniprot.org/citations/17548351 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/17548351 | http://purl.uniprot.org/core/pages | "24720-24730"xsd:string |
| http://purl.uniprot.org/citations/17548351 | http://purl.uniprot.org/core/title | "G Protein betagamma subunits augment UVB-induced apoptosis by stimulating the release of soluble heparin-binding epidermal growth factor from human keratinocytes."xsd:string |
| http://purl.uniprot.org/citations/17548351 | http://purl.uniprot.org/core/volume | "282"xsd:string |
| http://purl.uniprot.org/citations/17548351 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/17548351 |
| http://purl.uniprot.org/citations/17548351 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/17548351 |
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