Liang Ye, Mirnics Zeljka Korade, Yan Chaohua, Nylander Karen D, Schor Nina Felice
Pediatric Center for Neuroscience and Division of Child Neurology, University and Children's Hospital of Pittsburgh, Pittsburgh, PA 15213, USA.
Oncogene. 2003 Aug 21;22(35):5515-8. doi: 10.1038/sj.onc.1206844.
Bcl-2 is an antiapoptotic protein expressed in a wide variety of cell types. We have found that overexpression of bcl-2 in PC12 neural crest tumor cells leads to increased expression of neural differentiation-associated genes and decreased expression of proliferation-related genes. Culture growth rate decreases as well. Overexpression of bcl-2 also leads to increased expression of TrkA and increased phosphorylation of signal transductants in, albeit not specific for, the TrkA-MEK-ERK pathway. Blocking of NGF-mediated signaling through TrkA prevents Bcl-2-associated expression changes in differentiation-associated genes, raising the possibility that Bcl-2 mediates induction of neural differentiation through TrkA/NGF signaling.
Bcl-2是一种在多种细胞类型中表达的抗凋亡蛋白。我们发现，在PC12神经嵴肿瘤细胞中过表达bcl-2会导致神经分化相关基因的表达增加，增殖相关基因的表达减少。培养生长速率也会下降。bcl-2的过表达还会导致TrkA的表达增加以及TrkA-MEK-ERK通路中信号转导分子的磷酸化增加，尽管并非特异性针对该通路。通过TrkA阻断NGF介导的信号传导可防止Bcl-2相关的分化相关基因表达变化，这增加了Bcl-2通过TrkA/NGF信号传导介导神经分化诱导的可能性。
