Wills Z, Bateman J, Korey C A, Comer A, Van Vactor D
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Neuron. 1999 Feb;22(2):301-12. doi: 10.1016/s0896-6273(00)81091-0.
Genetic analysis of growth cone guidance choice points in Drosophila identified neuronal receptor protein tyrosine phosphatases (RPTPs) as key determinants of axon pathfinding behavior. We now demonstrate that the Drosophila Abl tyrosine kinase functions in the intersegmental nerve b (ISNb) motor choice point pathway as an antagonist of the RPTP Dlar. The function of Abl in this pathway is dependent on an intact catalytic domain. We also show that the Abl phosphoprotein substrate Enabled (Ena) is required for choice point navigation. Both Abl and Ena proteins associate with the Dlar cytoplasmic domain and serve as substrates for Dlar in vitro, suggesting that they play a direct role in the Dlar pathway. These data suggest that Dlar, Abl, and Ena define a phosphorylation state-dependent switch that controls growth cone behavior by transmitting signals at the cell surface to the actin cytoskeleton.
对果蝇生长锥导向选择点的遗传分析表明，神经元受体蛋白酪氨酸磷酸酶（RPTPs）是轴突寻路行为的关键决定因素。我们现在证明，果蝇Abl酪氨酸激酶在节间神经b（ISNb）运动选择点通路中作为RPTP Dlar的拮抗剂发挥作用。Abl在该通路中的功能依赖于完整的催化结构域。我们还表明，Abl磷酸化蛋白底物Enabled（Ena）是选择点导航所必需的。Abl和Ena蛋白都与Dlar细胞质结构域相关联，并在体外作为Dlar的底物，这表明它们在Dlar通路中发挥直接作用。这些数据表明，Dlar、Abl和Ena定义了一个磷酸化状态依赖性开关，该开关通过在细胞表面将信号传递到肌动蛋白细胞骨架来控制生长锥行为。
