Cholinergic Transactivation of the EGFR in HaCaT Keratinocytes Stimulates a Flotillin-1 Dependent MAPK-Mediated Transcriptional Response
Acetylcholine and its receptors regulate numerous cellular processes in keratinocytes and other non-neuronal cells. Muscarinic acetylcholine receptors are capable of transactivating the epidermal growth factor receptor (EGFR) and, downstream thereof, the mitogen-activated protein kinase (MAPK) casca...
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doaj-d7cea646692e455ca910c175176ca27c2020-11-24T21:57:44ZengMDPI AGInternational Journal of Molecular Sciences1422-00672015-03-011636447646310.3390/ijms16036447ijms16036447Cholinergic Transactivation of the EGFR in HaCaT Keratinocytes Stimulates a Flotillin-1 Dependent MAPK-Mediated Transcriptional ResponseSina Kühne0Wymke Ockenga1Antje Banning2Ritva Tikkanen3Institute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, D-35392 Giessen, GermanyInstitute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, D-35392 Giessen, GermanyInstitute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, D-35392 Giessen, GermanyInstitute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, D-35392 Giessen, GermanyAcetylcholine and its receptors regulate numerous cellular processes in keratinocytes and other non-neuronal cells. Muscarinic acetylcholine receptors are capable of transactivating the epidermal growth factor receptor (EGFR) and, downstream thereof, the mitogen-activated protein kinase (MAPK) cascade, which in turn regulates transcription of genes involved in cell proliferation and migration. We here show that cholinergic stimulation of human HaCaT keratinocytes results in increased transcription of matrix metalloproteinase MMP-3 as well as several ligands of the epidermal growth factor family. Since both metalloproteinases and the said ligands are involved in the transactivation of the EGFR, this transcriptional upregulation may provide a positive feed-forward loop for EGFR/MAPK activation. We here also show that the cholinergic EGFR and MAPK activation and the upregulation of MMP-3 and EGF-like ligands are dependent on the expression of flotillin-1 which we have previously shown to be a regulator of MAPK signaling.http://www.mdpi.com/1422-0067/16/3/6447acetylcholinemuscarinic receptormitogen-activated protein kinasecell proliferationreceptor tyrosine kinasesgrowth factorkeratinocytesgene regulation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sina Kühne Wymke Ockenga Antje Banning Ritva Tikkanen |
spellingShingle |
Sina Kühne Wymke Ockenga Antje Banning Ritva Tikkanen Cholinergic Transactivation of the EGFR in HaCaT Keratinocytes Stimulates a Flotillin-1 Dependent MAPK-Mediated Transcriptional Response International Journal of Molecular Sciences acetylcholine muscarinic receptor mitogen-activated protein kinase cell proliferation receptor tyrosine kinases growth factor keratinocytes gene regulation |
author_facet |
Sina Kühne Wymke Ockenga Antje Banning Ritva Tikkanen |
author_sort |
Sina Kühne |
title |
Cholinergic Transactivation of the EGFR in HaCaT Keratinocytes Stimulates a Flotillin-1 Dependent MAPK-Mediated Transcriptional Response |
title_short |
Cholinergic Transactivation of the EGFR in HaCaT Keratinocytes Stimulates a Flotillin-1 Dependent MAPK-Mediated Transcriptional Response |
title_full |
Cholinergic Transactivation of the EGFR in HaCaT Keratinocytes Stimulates a Flotillin-1 Dependent MAPK-Mediated Transcriptional Response |
title_fullStr |
Cholinergic Transactivation of the EGFR in HaCaT Keratinocytes Stimulates a Flotillin-1 Dependent MAPK-Mediated Transcriptional Response |
title_full_unstemmed |
Cholinergic Transactivation of the EGFR in HaCaT Keratinocytes Stimulates a Flotillin-1 Dependent MAPK-Mediated Transcriptional Response |
title_sort |
cholinergic transactivation of the egfr in hacat keratinocytes stimulates a flotillin-1 dependent mapk-mediated transcriptional response |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2015-03-01 |
description |
Acetylcholine and its receptors regulate numerous cellular processes in keratinocytes and other non-neuronal cells. Muscarinic acetylcholine receptors are capable of transactivating the epidermal growth factor receptor (EGFR) and, downstream thereof, the mitogen-activated protein kinase (MAPK) cascade, which in turn regulates transcription of genes involved in cell proliferation and migration. We here show that cholinergic stimulation of human HaCaT keratinocytes results in increased transcription of matrix metalloproteinase MMP-3 as well as several ligands of the epidermal growth factor family. Since both metalloproteinases and the said ligands are involved in the transactivation of the EGFR, this transcriptional upregulation may provide a positive feed-forward loop for EGFR/MAPK activation. We here also show that the cholinergic EGFR and MAPK activation and the upregulation of MMP-3 and EGF-like ligands are dependent on the expression of flotillin-1 which we have previously shown to be a regulator of MAPK signaling. |
topic |
acetylcholine muscarinic receptor mitogen-activated protein kinase cell proliferation receptor tyrosine kinases growth factor keratinocytes gene regulation |
url |
http://www.mdpi.com/1422-0067/16/3/6447 |
work_keys_str_mv |
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