Bixby J L, Jhabvala P
Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Florida 33136.
J Neurobiol. 1992 Jul;23(5):468-80. doi: 10.1002/neu.480230503.
Protein tyrosine kinases (PTKs) have major roles in signal transduction and growth control. There are several lines of evidence implicating PTKs in the regulation of axon growth, and this has led to the suggestion that they are centrally involved in the transduction of neuronal growth signals. To test this idea, we assayed the effect of the compounds genistein and lavendustin, specific inhibitors of PTKs, on neurite growth. We find that genistein greatly reduces phosphotyrosine in neurons, as expected from its action on other cells. Surprisingly, administration of genistein or lavendustin potentiated substrate-induced neurite growth in at least several different neuronal types. Stimulation of neurite growth by genistein was abolished by vanadate, providing additional evidence that inhibition of PTKs is responsible for this effect. The potentiation of growth is rather general, in that it occurs on several different extracellular matrix substrates and on two different cell adhesion molecules. Both the initiation of neurite growth and the rate of neurite elongation appear to be potentiated. Our results do not provide evidence for models of substrate-induced signal transduction that involve PTKs as a positive and necessary step, but suggest that such kinases play a regulatory role in neurite elongation.
蛋白质酪氨酸激酶（PTKs）在信号转导和生长控制中起主要作用。有几条证据表明PTKs参与轴突生长的调节，这导致有人提出它们在神经元生长信号的转导中起核心作用。为了验证这一想法，我们检测了PTKs的特异性抑制剂染料木黄酮和拉文达ustin对神经突生长的影响。我们发现，正如其对其他细胞的作用所预期的那样，染料木黄酮大大降低了神经元中的磷酸酪氨酸。令人惊讶的是，给予染料木黄酮或拉文达ustin能增强至少几种不同神经元类型中底物诱导的神经突生长。钒酸盐消除了染料木黄酮对神经突生长的刺激作用，这提供了额外的证据表明PTKs的抑制是这种效应的原因。生长的增强相当普遍，因为它发生在几种不同的细胞外基质底物和两种不同的细胞粘附分子上。神经突生长的起始和神经突伸长的速率似乎都得到了增强。我们的结果没有为涉及PTKs作为正向和必要步骤的底物诱导信号转导模型提供证据，但表明此类激酶在神经突伸长中起调节作用。
