Premium
The m1 muscarinic acetylcholine receptor transactivates the EGF receptor to modulate ion channel activity
Author(s) -
Tsai William,
Morielli Anthony D.,
Peralta Ernest G.
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.15.4597
Subject(s) - biology , receptor tyrosine kinase , transactivation , muscarinic acetylcholine receptor m5 , microbiology and biotechnology , ror1 , tyrosine kinase , proto oncogene tyrosine protein kinase src , tropomyosin receptor kinase c , cancer research , signal transduction , platelet derived growth factor receptor , muscarinic acetylcholine receptor m3 , receptor , muscarinic acetylcholine receptor , biochemistry , growth factor , transcription factor , gene
Intracellular tyrosine kinases link the G protein‐coupled m1 muscarinic acetylcholine receptor (mAChR) to multiple cellular responses. However, the mechanisms by which m1 mAChRs stimulate tyrosine kinase activity and the identity of the kinases within particular signaling pathways remain largely unknown. We show that the epidermal growth factor receptor (EGFR), a single transmembrane receptor tyrosine kinase, becomes catalytically active and dimerized through an m1 mAChR‐regulated pathway that requires protein kinase C, but is independent of EGF. Finally, we demonstrate that transactivation of the EGFR plays a major role in a pathway linking m1 mAChRs to modulation of the Kv1.2 potassium channel. These results demonstrate a ligand‐independent mechanism of EGFR transactivation by m1 mAChRs and reveal a novel role for these growth factor receptors in the regulation of ion channels by G protein‐coupled receptors.