Journal article
Authors list: Ockenga, Wymke; Kühne, Sina; Bocksberger, Simone; Banning, Antje; Tikkanen, Ritva
Publication year: 2014
Pages: 21433-21454
Journal: International Journal of Molecular Sciences
Volume number: 15
Issue number: 11
ISSN: 1661-6596
eISSN: 1422-0067
Open access status: Gold
DOI Link: https://doi.org/10.3390/ijms151121433
Publisher: MDPI
Abstract:
Non-neuronal acetylcholine plays a substantial role in the human skin by influencing adhesion, migration, proliferation and differentiation of keratinocytes. These processes are regulated by the Mitogen-Activated Protein (MAP) kinase cascade. Here we show that in HaCaT keratinocytes all five muscarinic receptor subtypes are expressed, but M-1 and M-3 are the subtypes involved in mitogenic signaling. Stimulation with the cholinergic agonist carbachol leads to activation of the MAP kinase extracellular signal regulated kinase, together with the protein kinase Akt. The activation is fully dependent on the transactivation of the epidermal growth factor receptor (EGFR), which even appears to be the sole pathway for the muscarinic receptors to facilitate MAP kinase activation in HaCaT cells. The transactivation pathway involves a triple-membrane-passing process, based on activation of matrix metalloproteases, and extracellular ligand release; whereas phosphatidylinositol 3-kinase, Src family kinases or protein kinase C do not appear to be involved in MAP kinase activation. Furthermore, phosphorylation, ubiquitination and endocytosis of the EGF receptor after cholinergic transactivation are different from that induced by a direct stimulation with EGF, suggesting that ligands other than EGF itself mediate the cholinergic transactivation.
Citation Styles
Harvard Citation style: Ockenga, W., Kühne, S., Bocksberger, S., Banning, A. and Tikkanen, R. (2014) Epidermal Growth Factor Receptor Transactivation Is Required for Mitogen-Activated Protein Kinase Activation by Muscarinic Acetylcholine Receptors in HaCaT Keratinocytes, International Journal of Molecular Sciences, 15(11), pp. 21433-21454. https://doi.org/10.3390/ijms151121433
APA Citation style: Ockenga, W., Kühne, S., Bocksberger, S., Banning, A., & Tikkanen, R. (2014). Epidermal Growth Factor Receptor Transactivation Is Required for Mitogen-Activated Protein Kinase Activation by Muscarinic Acetylcholine Receptors in HaCaT Keratinocytes. International Journal of Molecular Sciences. 15(11), 21433-21454. https://doi.org/10.3390/ijms151121433
Keywords
COUPLED RECEPTORS; epidermal growth factor; G protein coupled receptor; INDUCED PROLIFERATION; keratinocytes; matrix metalloprotease; mitogen-activated protein kinase; NICOTINIC RECEPTOR; NONNEURONAL CHOLINERGIC SYSTEM; STIMULATES DNA-SYNTHESIS; T-84 CELLS; TRANSACTIVATION