Truncated trkB.T1 is dominant negative inhibitor of trkB.TK+-mediated cell survival
Truncated trkB.T1 is dominant negative inhibitor of trkB.TK+-mediated cell survival
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DOI：
10.1006/bbrc.2001.4296
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发表时间：
2001-02-09
影响因子：
3.1
通讯作者：
Castrén, E
中科院分区：
文献类型：
--
作者：
Haapasalo, A;Koponen, E;Castrén, E
截短的trkB. T1（T1）神经营养因子受体抑制全长trkB.TK+（TK+）信号传导。至少有两种可能的机制已经提出了这种作用：T1可以捕获配体或作为显性负性受体发挥作用。为了区分这些可能性，我们研究了稳定表达TK+的血清剥夺的PC 12-trkB细胞的存活，观察到PC 12-trkB细胞显示组成型trkB激酶活性，这导致细胞亚群在不存在添加的脑源性神经营养因子（BDNF）和血清的情况下存活。外源性BDNF显著增加细胞存活率，并且这种增加被BDNF中和抗体抑制。抗体处理对组成型TK+活性无影响。与酪氨酸激酶抑制剂K252 a类似，转染的T1完全抑制PC 12-trkB细胞中BDNF或组成型trkB激酶活性的存活。此外，T1与TK+免疫共沉淀，并抑制其自磷酸化的BDNF，这些数据表明，截短的T1抑制TK+信号转导的显性负作用。(C)北京：科学出版社.
Truncated trkB.T1 (T1) neurotrophin receptor inhibits full-length trkB.TK+ (TK+) signaling. At least two possible mechanisms have been proposed for this action: T1 could trap the ligand or function as a dominant negative receptor. To differentiate between these possibilities we have studied survival of serum-deprived PC12-trkB cells stably expressing TK+, PC12-trkB cells were observed to display constitutive trkB kinase activity which leads to survival of a cell subpopulation in the absence of added brain-derived neurotrophic factor (BDNF) and serum. Exogenous BDNF significantly increased cell survival, and this increase was inhibited by BDNF neutralizing antibody. The antibody treatment had no effect on the constitutive TK+ activity. Transfected T1 completely inhibited survival by BDNF or constitutive trkB kinase activity in PC12-trkB cells similarly to tyrosine kinase inhibitor K252a. In addition, T1 coimmunoprecipitated with TK+ and inhibited its autophosphorylation by BDNF, These data suggest that truncated T1 inhibits TK+ signaling by dominant negative action. (C) 2001 Academic Press.