THE TRKB TYROSINE PROTEIN-KINASE IS A RECEPTOR FOR BRAIN-DERIVED NEUROTROPHIC FACTOR AND NEUROTROPHIN-3
THE TRKB TYROSINE PROTEIN-KINASE IS A RECEPTOR FOR BRAIN-DERIVED NEUROTROPHIC FACTOR AND NEUROTROPHIN-3
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DOI：
10.1016/0092-8674(91)90628-c
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发表时间：
1991-07-26
期刊：
影响因子：
64.5
通讯作者：
BARBACID, M
中科院分区：
文献类型：
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作者：
KLEIN, R;NANDURI, V;BARBACID, M
trkB是一种酪氨酸蛋白激酶基因，与trk高度相关，trk是一种原癌基因，编码神经生长因子（NGF）和神经营养因子-3 （NT-3）受体。trkB的表达仅限于中枢和周围神经系统的结构，表明它也编码神经营养因子的受体。我们发现脑源性神经营养因子（BDNF）和NT-3，而不是NGF，可以诱导gp145trkB的酪氨酸快速磷酸化，gp145trkB是trkB编码的受体之一。BDNF和NT-3可以诱导表达gp145trkB的静止NIH 3T3细胞的DNA合成。共转染编码gp145trkB和BDNF或NT-3的质粒可导致受体NIH 3T3细胞的转化。在这些试验中，BDNF引起的反应至少比NT-3高两个数量级。最后，I-125-NT-3结合到表达gp145trkB的NIH 3T3细胞；NT-3和BDNF可参与结合，而NGF不参与。这些发现表明gp145trkB可能作为BDNF和NT-3的神经营养受体。
trkB is a tyrosine protein kinase gene highly related to trk, a proto-oncogene that encodes a receptor for nerve growth factor (NGF) and neurotrophin-3 (NT-3). trkB expression is confined to structures of the central and peripheral nervous systems, suggesting it also encodes a receptor for neurotrophic factors. Here we show that brain-derived neurotrophic factor (BDNF) and NT-3, but not NGF, can induce rapid phosphorylation on tyrosine of gp145trkB, one of the receptors encoded by trkB. BDNF and NT-3 can induce DNA synthesis in quiescent NIH 3T3 cells that express gp145trkB. Cotransfection of plasmids encoding gp145trkB and BDNF or NT-3 leads to transformation of recipient NIH 3T3 cells. In these assays, BDNF elicits a response at least two orders of magnitude higher than NT-3. Finally, I-125-NT-3 binds to NIH 3T3 cells expressing gp145trkB; binding can be competed by NT-3 and BDNF but not by NGF. These findings indicate that gp145trkB may function as a neurotrophic receptor for BDNF and NT-3.