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Gö 6976 Is a Potent Inhibitor of Neurotrophin‐Receptor Intrinsic Tyrosine Kinase
Author(s) -
Behrens M. Margarita,
Strasser Uta,
Choi D. W.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0720919.x
Subject(s) - neurotrophin , receptor tyrosine kinase , neurotrophin 3 , tropomyosin receptor kinase c , tyrosine kinase , microbiology and biotechnology , neuroscience , chemistry , receptor , platelet derived growth factor receptor , biology , biochemistry , neurotrophic factors , brain derived neurotrophic factor , growth factor
: We report here that addition of the protein kinase Cinhibitor Gö 6976 blocked neurotrophin‐inducedsignaling and autophosphorylation of neurotrophin‐specific tyrosine kinase(Trk) receptors, either Trk B in cortical neurons or Trk A in GT1‐1‐trk9cells. The effect of Gö 6976 on Trkautophosphorylation was not inhibited by 100μ M orthovanadate,suggesting that the block was not due to the activation of tyrosinephosphatases. Moreover, addition of 10‐100 n M concentrations of Gö 6976 inhibited either Trk B or Trk A intrinsic kinase activity in cell‐free assays. Gö 6976 also blocked the ability of brain‐derived neurotrophic factor to promote cortical neuronal survival and the ability of nerve growth factor to promote PC12 cell survival and differentiation. These results suggest that Gö 6976, besides its known inhibitory effects on lipid‐ and calcium‐dependent isoforms of protein kinase C, can also inhibit neurotrophin signaling by directly inhibiting the instrinsic Trk.