TRYPTOPHAN HYDROXYLASE GENE STRUCTURE AND REGULATION

这项研究项目将集中在组织结构和调控方面 编码色氨酸羟基酶(TPH)的基因是 血清素的合成。虽然TPH已知通过以下方式进行监管 蛋白激酶介导的磷酸化，这个关键酶也可能是 在基因表达水平上进行调控。使用寡核苷酸探针 基于克隆的松果体编码TPH的cDNA，我们可以从 中枢神经系统。我们已经证明，在5‘端，当 与克隆的松果体cDNA进行比较。此外，我们已经表明， 改变血清素水平的药物改变了稳态 TPH基因表达水平。我们现在建议获得基因组和中枢神经系统特异的cDNA. 目的：获得TPH特异性克隆，并研究其基因调控机制。 最后，我们将研究受体事件在 TPH基因表达水平的调控。

The research project will focus on the structure and regulation of the gene encoding tryptophan hydroxylase (TPH), the rate-limiting enzyme in the synthesis of serotonin. While TPH is known to be regulated through protein kinase-mediated phosphorylation, this key enzyme may also be regulated at the level of gene expression. Using oligonucleotide probes based on cloned, pineal cDNAs encoding TPH, we can detect mRNA from the CNS. We have shown that the CNS mRNA is altered at the 5' end when compared with the cloned, pineal cDNAs. Furthermore, we have shown that pharmacological agents which alter serontonin levels alter steady-state TPH mRNA levels. We now propose to obtain genomic- and CNS-specific cDNA- clones specific for TPH and to study the mechanism of gene regulation. Lastly, we will study the potential involvement of receptor events in the regulation of TPH mRNA levels.