GDNF family ligand dependent STAT3 activation is mediated by specific alternatively spliced isoforms of GFRα2 and RET
作者： Lihan Zhou , Heng-Phon Too
DOI: 10.1016/J.BBAMCR.2013.07.004
关键词: Neural cell adhesion molecule 、 Glial cell line-derived neurotrophic factor 、 Neurturin 、 GDNF family of ligands 、 Cancer research 、 STAT3 、 Biology 、 Phosphorylation 、 Tyrosine 、 Neurite
摘要: Neurturin (NRTN), a member of the GDNF family ligands (GFL), is currently investigated in series clinical trials for Parkinson's disease. NRTN signals through its cognate receptor GFRα2 and co-receptor RET to induce neurite outgrowth, but underlying mechanism remains be better understood. STAT3 was previously shown activated by oncogenic RET, independent ligand GFRα. In this study, we demonstrated that induced serine(727) not tyrosine(705) phosphorylation primary cortical neuron neuronal cell lines. Remarkably, found mediated specifically GFRα2c RET9 isoforms. Furthermore, serine tyrosine dominant negative mutant impaired indicative role as downstream mediator function. Similar NGF, P-Ser-STAT3 localized mitochondria nucleus. Mitochondrial further intimately involved outgrowth. Collectively, these findings hitherto unrecognized novel specific isoforms mediating activation transcription whereby
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