Ahmed S, Kozma R, Monfries C, Hall C, Lim H H, Smith P, Lim L
Institute of Molecular and Cellular Biology, National University of Singapore.
Biochem J. 1990 Dec 15;272(3):767-73. doi: 10.1042/bj2720767.
A human brain-specific cDNA encoding n-chimaerin, a protein of predicted molecular mass 34 kDa, has sequence identity with two different proteins: protein kinase C (PKC) at the N-terminus and BCR protein [product of the breakpoint-cluster-region (BCR) gene, involved in Philadelphia chromosome translocation] at the C-terminus [Hall, Monfries, Smith, Lim, Kozma, Ahmed, Vannaisungham, Leung & Lim (1990) J. Mol. Biol. 211, 11-16]. The sequence identity of n-chimaerin with PKC includes the cysteine-rich motif CX2CX13CX2CX7CX7C, and amino acids upstream of the first cysteine residue, but not the kinase domain. This region of PKC has been implicated in the binding of diacylglycerol and phorbol esters in a phospholipid-dependent fashion. Part of this cysteine-rich motif (CX2CX13CX2C) has the potential of forming a 'Zn-finger' structure. Phorbol esters cause a variety of physiological changes and are among the most potent tumour promoters that have been described. PKC is the only known protein target for these compounds. We now report that n-chimaerin cDNA encodes a novel phospholipid-dependent phorbol ester receptor, with the cysteine-rich region being responsible for this activity. This finding has wide implications for previous studies equating phorbol ester binding with the presence of PKC in the brain.
一种编码n-嵌合蛋白的人脑特异性cDNA，其预测分子量为34 kDa，与两种不同的蛋白质具有序列同一性：N端与蛋白激酶C（PKC）相同，C端与BCR蛋白（断点簇区域（BCR）基因的产物，参与费城染色体易位）相同[霍尔、蒙弗里斯、史密斯、林、科兹马、艾哈迈德、万奈松哈姆、梁和林（1990年）《分子生物学杂志》211卷，第11 - 16页]。n-嵌合蛋白与PKC的序列同一性包括富含半胱氨酸的基序CX2CX13CX2CX7CX7C，以及第一个半胱氨酸残基上游的氨基酸，但不包括激酶结构域。PKC的这一区域已被认为以磷脂依赖性方式参与二酰基甘油和佛波酯的结合。这个富含半胱氨酸的基序的一部分（CX2CX13CX2C）具有形成“锌指”结构的潜力。佛波酯会引起多种生理变化，是已被描述的最有效的肿瘤促进剂之一。PKC是这些化合物唯一已知的蛋白质靶点。我们现在报告n-嵌合蛋白cDNA编码一种新型的磷脂依赖性佛波酯受体，富含半胱氨酸的区域负责这种活性。这一发现对以往将脑内佛波酯结合等同于PKC存在的研究具有广泛的意义。
