Regulation of TRPM8 channel activity by Src-mediated tyrosine phosphorylation
- Manolache, Alexandra Department of Anatomy, Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucuresti, Romania
- Selescu, Tudor Department of Anatomy, Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucuresti, Romania
- Maier, G. Larisa Department of Anatomy, Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucuresti, Romania - Department of Biology, University of Fribourg, Switzerland
- Mentel, Mihaela Department of Enzymology, Institute of Biochemistry of the Romanian Academy, Bucuresti, Romania - Regional Institute of Oncology, TRANSCEND Center, Iasi, Romania
- Ionescu, Aura Elena Department of Enzymology, Institute of Biochemistry of the Romanian Academy, Bucuresti, Romania
- Neacsu, Cristian Department of Anatomy, Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucuresti, Romania - Department of Life and Environmental Sciences, Horia Hulubei National Institute for Research and Development in Physics and Nuclear Engineering (IFIN‐HH), Măgurele, Romania
- Babes, Alexandru Department of Anatomy, Physiology and Biophysics, Faculty of Biology, University of Bucharest, Bucuresti, Romania
- Szedlacsek, Stefan Eugen Department of Enzymology, Institute of Biochemistry of the Romanian Academy, Bucuresti, Romania
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2019
Published in:
- Journal of Cellular Physiology. - 2020, vol. 235, no. 6, p. 5192-5203
English
The transient receptor potential melastatin type 8 (TRPM8) receptor channel is expressed in primary afferent neurons where it is the main transducer of innocuous cold temperatures and also in a variety of tumors, where it is involved in progression and metastasis. Modulation of this channel by intracellular signaling pathways has therefore important clinical implications. We investigated the modulation of recombinant and natively expressed TRPM8 by the Src kinase, which is known to be involved in cancer pathophysiology and inflammation. Human TRPM8 expressed in HEK293T cells is constitutively tyrosine phosphorylated by Src which is expressed either heterologously or endogenously. Src action on TRPM8 potentiates its activity, as treatment with PP2, a selective Src kinase inhibitor, reduces both TRPM8 tyrosine phosphorylation and cold‐induced channel activation. RNA interference directed against the Src kinase diminished the extent of PP2‐induced functional downregulation of TRPM8, confirming that PP2 acts mainly through Src inhibition. Finally, the effect of PP2 on TRPM8 cold activation was reproduced in cultured rat dorsal root ganglion neurons, and this action was antagonized by the protein tyrosine phosphatase inhibitor pervanadate, confirming that TRPM8 activity is sensitive to the cellular balance between tyrosine kinases and phosphatases. This positive modulation of TRPM8 by Src kinase may be relevant for inflammatory pain and cancer signaling.
- Faculty
- Faculté des sciences et de médecine
- Department
- Département de Biologie
- Language
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- English
- Classification
- Biological sciences
- License
- License undefined
- Identifiers
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- RERO DOC 327678
- DOI 10.1002/jcp.29397
- Persistent URL
- https://folia.unifr.ch/unifr/documents/308299
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