HUMAN BRAIN N-CHIMAERIN CDNA ENCODES A NOVEL PHORBOL ESTER RECEPTOR
HUMAN BRAIN N-CHIMAERIN CDNA ENCODES A NOVEL PHORBOL ESTER RECEPTOR
复制标题
DOI：
10.1042/bj2720767
复制
发表时间：
1990-12-15
影响因子：
4.1
通讯作者：
LIM, L
中科院分区：
文献类型：
--
作者：
AHMED, S;KOZMA, R;LIM, L
编码n-嵌合蛋白（一种预测分子量为34 kDa的蛋白质）的人脑特异性cDNA与两种不同的蛋白质具有序列同一性：N-末端的蛋白激酶C（PKC）和C-末端的BCR蛋白[断裂点簇区（BCR）基因的产物，参与费城染色体易位][Hall，Monfries，Smith，Lim，Kozma，Ahmed，Vannaisungham，Leung & Lim（1990）J. Mol. 211，11-16]。N-嵌合蛋白与PKC的序列同一性包括富含半胱氨酸的基序CX 2CX 13 CX 2CX 7 CX 7 C和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的这一区域以磷脂依赖性方式参与甘油二酯和佛波酯的结合。该富含半胱氨酸的基序（CX 2CX 13 CX 2C）的一部分具有形成“锌指”结构的潜力。佛波酯引起多种生理变化，并且是已经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编码一种新的磷脂依赖性佛波酯受体，半胱氨酸丰富的区域负责这种活动。这一发现对以前将佛波酯结合等同于大脑中PKC存在的研究具有广泛的意义。
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.