Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing
Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing
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DOI：
10.1523/jneurosci.20-02-00639.2000
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发表时间：
2000-01-15
影响因子：
5.3
通讯作者：
Douglass, J
中科院分区：
文献类型：
--
作者：
Fricker, LD;McKinzie, AA;Douglass, J
在缺乏活性羧肽酶E（一种神经肽加工酶）的小鼠大脑中鉴定出了五种新型肽。这些肽由一种单一的前体产生，该前体被称为proSAAS，它存在于人类、小鼠和大鼠中。ProSAAS mRNA主要在大脑和其他神经内分泌组织（垂体、肾上腺、胰腺）中表达；在大脑内，该mRNA在神经元中广泛分布。当在AtT - 20细胞中表达时，proSAAS通过调节途径分泌，并且还在成对碱性切割位点被加工成较小的肽。在AtT - 20细胞中过表达proSAAS会大幅降低内源性前激素阿黑皮素原的加工速率。纯化的proSAAS抑制前激素转化酶1的活性，半数抑制浓度（IC50）为590 nM，但不抑制前激素转化酶2。综上所述，proSAAS可能是前激素转化酶1的一种内源性抑制剂。
Five novel peptides were identified in the brains of mice lacking active carboxypeptidase E, a neuropeptide-processing enzyme. These peptides are produced from a single precursor, termed proSAAS, which is present in human, mouse, and rat. ProSAAS mRNA is expressed primarily in brain and other neuroendocrine tissues (pituitary, adrenal, pancreas); within brain, the mRNA is broadly distributed among neurons. When expressed in AtT-20 cells, proSAAS is secreted via the regulated pathway and is also processed at paired-basic cleavage sites into smaller peptides. Overexpression of proSAAS in the AtT-20 cells substantially reduces the rate of processing of the endogenous prohormone proopiomelanocortin. Purified proSAAS inhibits prohormone convertase 1 activity with an IC50 of 590 nM but does not inhibit prohormone convertase 2. Taken together, proSAAS may represent an endogenous inhibitor of prohormone convertase 1.