Journalartikel

Jahr der Veröffentlichung: 2014

Seiten: 21433-21454

Zeitschrift: International Journal of Molecular Sciences

Bandnummer: 15

Heftnummer: 11

ISSN: 1661-6596

eISSN: 1422-0067

Open Access Status: Gold

DOI Link: https://doi.org/10.3390/ijms151121433

Verlag: 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.

Harvard-Zitierstil: 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-Zitierstil: 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