Human melanoma TrkC: Its association with a purine-analog-sensitive kinase activity

Dario Marchetti, Brian Murry, Jennifer Galjour, Andrea Wilke-Greiter

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The various members of the Trk tyrosine kinase family and p75 neurotrophin receptor (p75NTR) have been identified as signaling receptors for the structurally related members of the neurotrophins (NT) family. We have previously reported that NT treatment of murine and human brain-metastatic melanoma cells affects their invasive capacities and increases the production of extracellular-matrix degradative enzymes. These cells express aberrant levels of functional p75NTR and TrkC, the putative high-affinity receptor for the neurotrophin NT-3. Here we demonstrate that, by using sensitive immune-complex kinase assays in human brain-metastatic (70W) melanoma cells, TrkC receptors associate with a kinase activity exhibiting a dose-dependent susceptibility to inhibition by the purine-analogs 6-thioguanine and 2-aminopurine. The activity of this purine-analog-sensitive kinase (PASK) was induced by NT-3 in a time-dependent fashion, phosphorylating exogenous myelin basic protein (MBP) but not denatured enolase. It is similar to the one reported to relate with p75NTR and TrkA receptors and stimulated by the prototypic NT, nerve growth factor. Thus, PASKs may represent unique signaling components common to NT receptors that could engage joint downstream signaling effectors in brain-metastatic melanoma.

Original languageEnglish (US)
Pages (from-to)865-872
Number of pages8
JournalJournal of Cellular Biochemistry
Volume88
Issue number5
DOIs
StatePublished - Apr 1 2003

Keywords

  • 2-aminopurine (2-AP)
  • 6-thioguanine (6-TG)
  • Brain-metastatic melanoma
  • Neurotrophin receptors
  • Neurotrophins
  • Purine-analog-sensitive-kinase (PASK)
  • TrkC

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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