Identification of a receptor for Reg (Regenerating gene) protein, a pancreatic β-cell regeneration factor
Identification of a receptor for Reg (Regenerating gene) protein, a pancreatic β-cell regeneration factor
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DOI：
10.1074/jbc.275.15.10723
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发表时间：
2000-04-14
影响因子：
4.8
通讯作者：
Okamoto, H
中科院分区：
文献类型：
--
作者：
Kobayashi, S;Akiyama, T;Okamoto, H
Reg（再生基因）作为一个在再生胰岛中特异性表达的基因被分离出来(Terazono， K., Yamamoto， H., Takasawa， S., Shiga， K., Yonemura， Y., Tochino， Y., and Okamoto， H.（1988）。Reg基因产物，Reg/ Reg蛋白，已被证明在体外和体内刺激胰岛β细胞生长，并改善实验性糖尿病。在本研究中，我们从一个大鼠胰岛cDNA文库中分离了一个Reg蛋白受体的cDNA。该cDNA编码了一个细胞表面919个氨基酸的蛋白，该cDNA导入的细胞与Reg蛋白具有高亲和力。当将cDNA导入到rm5f细胞（一种表现出Reg依赖性生长的胰腺β细胞系）时，转化子表现出显著增加5'-溴-2'-脱氧尿苷的掺入以及响应Reg蛋白的细胞数量。同源性研究表明，该cDNA与人类多外生瘤样基因同源，其功能迄今尚不清楚。这些结果强烈表明，受体是由外生骨组织样基因编码的，并介导regg蛋白的生长信号，促进β细胞再生。
Reg (regenerating gene) was isolated as a gene specifically expressed in regenerating islets (Terazono, K., Yamamoto, H., Takasawa, S., Shiga, K., Yonemura, Y., Tochino, Y., and Okamoto, H. (1988) J. Biol. Chem, 263, 2111-2114), Rat and human Reg gene products, Reg/REG proteins, have been demonstrated to stimulate islet beta-cell growth in vitro and in vivo and to ameliorate experimental diabetes. In the present study, we isolated a cDNA for the Reg protein receptor from a rat islet cDNA library. The cDNA encoded a cell surface 919-amino acid protein, and the cells into which the cDNA had been introduced bound Reg protein with high affinity. When the cDNA was introduced into RINm5F cells, a pancreatic beta-cell line that shows Reg-dependent growth, the transformants exhibited significant increases in the incorporation of 5'-bromo-2'-deoxyuridine as well as in the cell numbers in response to Reg protein. A homology search revealed that the cDNA is a homologue to a human multiple exostoses-like gene, the function of which has hitherto been unknown. These results strongly suggest that the receptor is encoded by the exostoses-like gene and mediates a growth signal of Reg protein for beta-cell regeneration.