酪氨酸蛋白激酶B是脑源性神经营养因子和神经营养因子-3的受体。
The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3.
作者信息
Klein R, Nanduri V, Jing S A, Lamballe F, Tapley P, Bryant S, Cordon-Cardo C, Jones K R, Reichardt L F, Barbacid M
机构信息
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
出版信息
Cell. 1991 Jul 26;66(2):395-403. doi: 10.1016/0092-8674(91)90628-c.
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, 125I-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.
TrkB是一种与Trk高度相关的酪氨酸蛋白激酶基因，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）的受体。TrkB的表达局限于中枢和外周神经系统结构，这表明它也编码一种神经营养因子受体。在此我们表明，脑源性神经营养因子（BDNF）和NT-3，而非NGF，能够诱导由TrkB编码的受体之一gp145TrkB的酪氨酸快速磷酸化。BDNF和NT-3能够在表达gp145TrkB的静止NIH 3T3细胞中诱导DNA合成。共转染编码gp145TrkB和BDNF或NT-3的质粒会导致受体NIH 3T3细胞发生转化。在这些试验中，BDNF引发的反应比NT-3至少高两个数量级。最后，125I-NT-3与表达gp145TrkB的NIH 3T3细胞结合；这种结合可被NT-3和BDNF竞争，但不能被NGF竞争。这些发现表明，gp145TrkB可能作为BDNF和NT-3的神经营养受体发挥作用。
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