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Int. J. Mol. Sci. 2015, 16(3), 6447-6463; doi:10.3390/ijms16036447

Cholinergic Transactivation of the EGFR in HaCaT Keratinocytes Stimulates a Flotillin-1 Dependent MAPK-Mediated Transcriptional Response

Institute of Biochemistry, Medical Faculty, University of Giessen, Friedrichstrasse 24, D-35392 Giessen, Germany
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Academic Editor: Kathleen Van Craenenbroeck
Received: 23 February 2015 / Revised: 6 March 2015 / Accepted: 17 March 2015 / Published: 20 March 2015
(This article belongs to the Collection G Protein-Coupled Receptor Signaling and Regulation)
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Abstract

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. View Full-Text
Keywords: acetylcholine; muscarinic receptor; mitogen-activated protein kinase; cell proliferation; receptor tyrosine kinases; growth factor; keratinocytes; gene regulation acetylcholine; muscarinic receptor; mitogen-activated protein kinase; cell proliferation; receptor tyrosine kinases; growth factor; keratinocytes; gene regulation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Kühne, S.; Ockenga, W.; Banning, A.; Tikkanen, R. Cholinergic Transactivation of the EGFR in HaCaT Keratinocytes Stimulates a Flotillin-1 Dependent MAPK-Mediated Transcriptional Response. Int. J. Mol. Sci. 2015, 16, 6447-6463.

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