Braks J A, Martens G J
Department of Animal Physiology, University of Nijmegen, The Netherlands.
Cell. 1994 Jul 29;78(2):263-73. doi: 10.1016/0092-8674(94)90296-8.
The neuroendocrine polypeptide 7B2 is a highly conserved secretory protein selectively present in prohormone-producing cells equipped with a regulated secretory pathway. We find that the amino-terminal half of 7B2 is distantly related to chaperonins, a subclass of molecular chaperones. When incubated in vitro with newly synthesized pituitary proteins, recombinant 7B2 specifically associates with prohormone convertase PC2. Metabolic cell labeling combined with coimmunoprecipitation studies showed that, in vivo, the precursor form of 7B2 interacts with the proform of PC2. Pulse-chase analysis revealed that this association is transient in that it commences early in the secretory pathway, while dissociation in the later stages appears to coincide with the cleavages of 7B2, proPC2, and prohormone. Our results suggest that 7B2 is a novel type of molecular chaperone preventing premature activation of proPC2 in the regulated secretory pathway.
神经内分泌多肽7B2是一种高度保守的分泌蛋白，选择性地存在于具有调节性分泌途径的激素原生成细胞中。我们发现7B2的氨基末端一半与分子伴侣的一个亚类伴侣蛋白有远缘关系。当与新合成的垂体蛋白在体外孵育时，重组7B2特异性地与激素原转化酶PC2结合。代谢细胞标记结合免疫共沉淀研究表明，在体内，7B2的前体形式与PC2的前体形式相互作用。脉冲追踪分析显示这种结合是短暂的，因为它在分泌途径的早期开始，而在后期的解离似乎与7B2、前PC2和激素原的切割同时发生。我们的结果表明，7B2是一种新型分子伴侣，可防止PC2在调节性分泌途径中过早激活。
