Constitutively active Src facilitates NGF‐induced phosphorylation of TrkA and causes enhancement of the MAPK signaling in SK‐N‐MC cells

FEBS Letters

Tsuruda, Akinori²  Maekawa, Takaaki³  Suzuki, Shingo¹  Oka, Syuichi² 

[1] Institute for Protein Research, University of Osaka, Suita, Osaka 565-0871, Japan;Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology (AIST), Central 6, Tsukuba, Ibaraki 305-8566, Japan;Institute of Agricultural and Forest Engineering, Food and Bioresource Process Engineering Laboratory, University of Tsukuba, Tsukuba, Ibaraki 305-8572, Japan

关键词: Src;    TrkA;    Grb2;    Nerve growth factor;    Mitogen-activated protein kinase;    SK-N-MC cell;    NGF;    nerve growth factor;    MAPK;    mitogen-activated protein kinase;    ERK;    extracellular signal-regulated kinase;    SFK;    Src family kinase;    RTK;    receptor tyrosine kinase;    EGFR;    epidermal growth factor receptor;    PDGFR;    platelet-derived growth factor receptor;   

DOI  :  10.1016/S0014-5793(04)00115-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown