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G Protein betagamma subunits augment UVB-induced apoptosis by stimulating the release of soluble heparin-binding epidermal growth factor from human keratinocytes
DC Field | Value | Language |
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dc.contributor.author | Seo, Miran | - |
dc.contributor.author | Lee, Mi-Jeong | - |
dc.contributor.author | Heo, Jin Hee | - |
dc.contributor.author | Lee, Yun-Il | - |
dc.contributor.author | Kim, Yeni | - |
dc.contributor.author | Kim, So-Young | - |
dc.contributor.author | Lee, Eun-So | - |
dc.contributor.author | Juhnn, Yong-Sung | - |
dc.date.accessioned | 2010-07-08 | - |
dc.date.available | 2010-07-08 | - |
dc.date.issued | 2007-06-06 | - |
dc.identifier.citation | J Biol Chem. 282(34): 24720-24730 | en |
dc.identifier.issn | 0021-9258 (Print) | - |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17548351 | - |
dc.identifier.uri | https://hdl.handle.net/10371/68489 | - |
dc.description.abstract | 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. | en |
dc.language.iso | en | en |
dc.publisher | American Society for Biochemistry and Molecular Biology | en |
dc.subject | Cell Line, Tumor | en |
dc.subject | Culture Media, Conditioned/pharmacology | en |
dc.subject | Dose-Response Relationship, Drug | en |
dc.subject | Epidermal Growth Factor/*metabolism | en |
dc.subject | GTP-Binding Protein beta Subunits/chemistry/*physiology | en |
dc.subject | GTP-Binding Protein gamma Subunits/chemistry/*physiology | en |
dc.subject | Humans | en |
dc.subject | Intercellular Signaling Peptides and Proteins | en |
dc.subject | Keratinocytes/*metabolism/pathology | en |
dc.subject | Models, Biological | en |
dc.subject | Phosphorylation | en |
dc.subject | Protein Binding | en |
dc.subject | Receptor, Epidermal Growth Factor/metabolism | en |
dc.subject | p38 Mitogen-Activated Protein Kinases/metabolism | en |
dc.subject | src-Family Kinases/metabolism | en |
dc.subject | Apoptosis | - |
dc.subject | Ultraviolet Rays | - |
dc.title | G Protein betagamma subunits augment UVB-induced apoptosis by stimulating the release of soluble heparin-binding epidermal growth factor from human keratinocytes | en |
dc.type | Article | en |
dc.contributor.AlternativeAuthor | 서미란 | - |
dc.contributor.AlternativeAuthor | 이미정 | - |
dc.contributor.AlternativeAuthor | 허진희 | - |
dc.contributor.AlternativeAuthor | 이윤일 | - |
dc.contributor.AlternativeAuthor | 김예니 | - |
dc.contributor.AlternativeAuthor | 김소영 | - |
dc.contributor.AlternativeAuthor | 이은소 | - |
dc.contributor.AlternativeAuthor | 전용성 | - |
dc.identifier.doi | 10.1074/jbc.M702343200 | - |
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