On the Death Trk
On the Death Trk
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DOI：
10.1002/dneu.20769
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发表时间：
2010-04-01
影响因子：
3
通讯作者：
Fainzilber, Mike
中科院分区：
文献类型：
--
作者：
Harel, Liraz;Costa, Barbara;Fainzilber, Mike
受体酪氨酸激酶trk家族支持神经系统的存活和分化。奇怪的是，也已经表明trk家族的成员可以诱导神经元来源的儿科肿瘤细胞的细胞死亡。此外，TrkA和TrkC分别作为神经母细胞瘤和髓母细胞瘤的良好预后指标。虽然这些观察结果之间可能存在的联系很有趣，但直到最近，对所涉及的机制的了解仍然有限。最近的研究结果表明，TrkA可能通过刺激p75裂解影响神经细胞死亡。TrkA和CCM 2（脑海绵状血管畸形基因2的蛋白产物）之间新发现的相互作用提出了另一种p75独立机制。CCM 2与TrkA的共表达诱导髓母细胞瘤和神经母细胞瘤细胞的细胞死亡，并且CCM 2表达水平与TrkA的表达水平相关，并且在神经母细胞瘤患者中具有良好的预后。因此，trk诱导细胞死亡之谜的机制线索已经开始出现。详细阐明这些机制及其在体内的生理意义，将是未来研究的浓厚兴趣。(C)2010年威利期刊。Inc.开发神经生物学70：298-303，2010年
The trk family of receptor tyrosine kinases supports survival and differentiation in the nervous system. Paradoxically it has also been shown that members of the trk family can induce cell death in pediatric tumor cells of neuronal origin. Moreover, TrkA and TrkC serve as good prognostic indicators in neuroblastoma and medulloblatoma, respectively. Although the possible linkage between these observations was intriguing, until recently there was limited insight on the mechanisms involved. Recent findings suggest that TrkA might influence neuronal cell death through stimulation of p75 cleavage. An alternative p75-independent mechanism was suggested by a newly discovered interaction between TrkA and CCM2 (the protein product of the gene cerebral cavernous malformation 2). Coexpression of CCM2 with TrkA induces cell death in medulloblastoma and neuroblastoma cells, and CCM2 expression levels correlate with those of TrkA and with good prognosis in neuroblastoma patients. Thus, mechanistic clues to the enigma of trk-induced cell death have begun to emerge. Detailed elucidation of these mechanisms and their in vivo physiological significance will be of keen interest for future research. (C) 2010 Wiley Periodicals. Inc. Develop Neurobiol 70: 298-303, 2010