Extracellular UDP-glucose activates P2Y14 Receptor and Induces Signal Transducer and Activator of Transcription 3 (STAT3) Tyr705 phosphorylation and binding to hyaluronan synthase 2 (HAS2) promoter, stimulating hyaluronan synthesis of keratinocytes
| Autor: | Jarmo T. Laitinen, Raija Tammi, Katri M. Makkonen, Riikka Kärnä, Tiina A. Jokela, Markku Tammi |
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| Rok vydání: | 2014 |
| Předmět: |
Keratinocytes
STAT3 Transcription Factor Uridine Diphosphate Glucose endocrine system Response element Amino Acid Motifs Glycobiology and Extracellular Matrices Biology Hyaluronan Synthase 2 Biochemistry chemistry.chemical_compound Cell Movement Hyaluronic acid medicine Humans Keratinocyte migration Glucuronosyltransferase Hyaluronic Acid Phosphorylation Promoter Regions Genetic Molecular Biology Transcription factor integumentary system Receptors Purinergic P2 Cell Biology Janus Kinase 2 Molecular biology Up-Regulation carbohydrates (lipids) medicine.anatomical_structure chemistry Tyrosine Signal transduction Keratinocyte Hyaluronan Synthases Protein Binding Signal Transduction |
| Zdroj: | The Journal of biological chemistry. 289(26) |
| ISSN: | 1083-351X |
| Popis: | Hyaluronan, a major matrix molecule in epidermis, is often increased by stimuli that enhance keratinocyte proliferation and migration. We found that small amounts of UDP-sugars were released from keratinocytes and that UDP-glucose (UDP-Glc) added into keratinocyte cultures induced a specific, rapid induction of hyaluronan synthase 2 (HAS2), and an increase of hyaluronan synthesis. The up-regulation of HAS2 was associated with JAK2 and ERK1/2 activation, and specific Tyr(705) phosphorylation of transcription factor STAT3. Inhibition of JAK2, STAT3, or Gi-coupled receptors blocked the induction of HAS2 expression by UDP-Glc, the latter inhibitor suggesting that the signaling was triggered by the UDP-sugar receptor P2Y14. Chromatin immunoprecipitations demonstrated increased promoter binding of Tyr(P)(705)-STAT3 at the time of HAS2 induction. Interestingly, at the same time Ser(P)(727)-STAT3 binding to its response element regions in the HAS2 promoter was unchanged or decreased. UDP-Glc also stimulated keratinocyte migration, proliferation, and IL-8 expression, supporting a notion that UDP-Glc signals for epidermal inflammation, enhanced hyaluronan synthesis as an integral part of it. |
| Databáze: | OpenAIRE |
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