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Constitutively active Src facilitates NGF‐induced phosphorylation of TrkA and causes enhancement of the MAPK signaling in SK‐N‐MC cells
Author(s) -
Tsuruda Akinori,
Suzuki Shingo,
Maekawa Takaaki,
Oka Syuichi
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(04)00115-2
Subject(s) - tropomyosin receptor kinase a , proto oncogene tyrosine protein kinase src , nerve growth factor , mapk/erk pathway , phosphorylation , low affinity nerve growth factor receptor , microbiology and biotechnology , kinase , chemistry , grb2 , cancer research , biology , receptor , biochemistry
Here we investigated a biological association of constitutively active Src with TrkA in SK‐N‐MC human neuroblastoma cells. Activation of TrkA and extracellular signal‐regulated kinase (ERK) by nerve growth factor (NGF) was inhibited by pretreatment with PP2, an inhibitor of Src family kinases. Moreover, NGF‐induced phosphorylation of TrkA and ERK was also attenuated by the transfection with a dominant‐negative src construct. On the other hand, the transfection with a constitutively active src construct enhanced these phosphorylations. In addition, we showed that active Src phosphorylates TrkA directly in vitro, and that Src associates with TrkA through Grb2 after NGF stimulation. These results suggest that constitutively active Src that associates with TrkA through Grb2 after NGF stimulation participates in TrkA phosphorylation and in turn enhances the mitogen‐activated protein kinase signaling in SK‐N‐MC cells.