TY  - JOUR
A1  - Ockenga, Wymke
A1  - Kühne, Sina
A1  - Bocksberger, Simone
A1  - Banning, Antje
A1  - Tikkanen, Ritva
T1  - Epidermal growth factor receptor transactivation is required for mitogen-activated protein kinase activation by muscarinic acetylcholine receptors in HaCaT keratinocytes
T2  - International journal of molecular sciences
N2  - 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 M1 and M3 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.
KW  - G protein coupled receptor
KW  - epidermal growth factor
KW  - acetylcholine
KW  - muscarinic receptor
KW  - transactivation
KW  - mitogen-activated protein kinase
KW  - keratinocytes
KW  - matrix metalloprotease
Y1  - 2014
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/39401
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-394019
SN  - 1422-0067
N1  - © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
VL  - 15
IS  - 11
SP  - 21433
EP  - 21454
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  -