<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Manolache, Alexandra</dc:creator>
  <dc:creator>Selescu, Tudor</dc:creator>
  <dc:creator>Maier, G. Larisa</dc:creator>
  <dc:creator>Mentel, Mihaela</dc:creator>
  <dc:creator>Ionescu, Aura Elena</dc:creator>
  <dc:creator>Neacsu, Cristian</dc:creator>
  <dc:creator>Babes, Alexandru</dc:creator>
  <dc:creator>Szedlacsek, Stefan Eugen</dc:creator>
  <dc:date>2019</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">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.</dc:description>
  <dc:format>application/pdf</dc:format>
  <dc:identifier>https://folia.unifr.ch/global/documents/308299</dc:identifier>
  <dc:identifier>https://folia.unifr.ch/documents/308299/files/mai_rtc.pdf</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.1002/jcp.29397</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:rights>License undefined</dc:rights>
  <dc:source>Journal of Cellular Physiology. - 2020, vol. 235, no. 6, p. 5192-5203</dc:source>
  <dc:subject>info:eu-repo/classification/udc/57</dc:subject>
  <dc:title xmlns:ns1="xml" ns1:lang="en">Regulation of TRPM8 channel activity by Src-mediated tyrosine phosphorylation</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>