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Extracellular Signal‐Regulated Protein Kinase, c‐Jun N‐Terminal Protein Kinase, and Calcineurin Regulate Transient Receptor Potential M3 (TRPM3) Induced Activation of AP‐1
Author(s) -
Lesch Andrea,
Rössler Oliver G.,
Thiel Gerald
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25904
Subject(s) - microbiology and biotechnology , calcineurin , chemistry , mitogen activated protein kinase kinase , map kinase kinase kinase , extracellular , ask1 , extracellular signal regulated kinases , kinase , protein kinase a , biology , medicine , transplantation
Stimulation of transient receptor potential M3 (TRPM3) cation channels with pregnenolone sulfate induces an influx of Ca 2+ ions into the cells and a rise in the intracellular Ca 2+ concentration, leading to the activation of the activator protein‐1 (AP‐1) transcription factor. Here, we show that expression of a constitutively active mutant of the Ca 2+ /calmodulin‐dependent protein phosphatase calcineurin attenuated pregnenolone sulfate‐induced AP‐1 activation in TRPM3‐expressing cells. Likewise, expression of the regulatory B subunit of calcineurin reduced AP‐1 activity in the cells following stimulation of TRPM3 channels. MAP kinase phosphatase‐1 has been shown to attenuate TRPM3‐mediated AP‐1 activation. Here, we show that pregnenolone sulfate‐induced stimulation of TRPM3 triggers the phosphorylation and activation of the MAP kinase extracellular signal‐regulated protein kinase (ERK1/2). Pharmacological and genetic experiments revealed that stimulation of ERK1/2 is essential for the activation of AP‐1 in cells expressing stimulated TRPM3 channels. ERK1/2 is required for the activation of the transcription factor c‐Jun, a key component of the AP‐1 transcription factor, and regulates c‐Fos promoter activity. In addition, we identified c‐Jun N‐terminal protein kinase (JNK1/2) as a second signal transducer of activated TRPM3 channels. Together, the data show that calcineurin and the protein kinases ERK1/2 and JNK1/2 are important regulators within the signaling cascade connecting TRPM3 channel stimulation with increased AP‐1‐regulated transcription. J. Cell. Biochem. 118: 2409–2419, 2017. © 2017 Wiley Periodicals, Inc.