TY - JOUR
T1 - Human melanoma TrkC
T2 - Its association with a purine-analog-sensitive kinase activity
AU - Marchetti, Dario
AU - Murry, Brian
AU - Galjour, Jennifer
AU - Wilke-Greiter, Andrea
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/4/1
Y1 - 2003/4/1
N2 - 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.
AB - 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.
KW - 2-aminopurine (2-AP)
KW - 6-thioguanine (6-TG)
KW - Brain-metastatic melanoma
KW - Neurotrophin receptors
KW - Neurotrophins
KW - Purine-analog-sensitive-kinase (PASK)
KW - TrkC
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U2 - 10.1002/jcb.10473
DO - 10.1002/jcb.10473
M3 - Article
C2 - 12616526
AN - SCOPUS:0037376691
SN - 0730-2312
VL - 88
SP - 865
EP - 872
JO - Journal of Cellular Biochemistry
JF - Journal of Cellular Biochemistry
IS - 5
ER -