Cloning, nucleotide sequence, and chromosome localization of the human pleiotrophin gene.
Cloning, nucleotide sequence, and chromosome localization of the human pleiotrophin gene.
复制标题
人类多效蛋白基因的克隆、核苷酸序列和染色体定位。
DOI：
10.1021/bi00163a009
复制
发表时间：
1992
期刊：
影响因子：
2.9
通讯作者：
Kumar,BV
中科院分区：
文献类型：
--
作者：
Milner,PG;Shah,D;Veile,R;Donis-Keller,H;Kumar,BV
1992年9月11日收到的修订稿摘要：促性腺激素(PTN)、中期因子(MK)和维甲酸诱导的肝素结合蛋白(RI-HB)是最近发现的发育调节细胞因子家族的成员。我们报道了人类PTN基因基因组版的克隆、测序、染色体定位和结构组织，并将其与小鼠的MK基因进行了比较。发现PTN基因由5个外显子和4个内含子组成，与小鼠的MK基因相似。外显子1与MK一样，似乎不编码氨基酸序列。与MK基因的情况一样，外显子2编码PTN的疏水前导序列，这构成了基因翻译的开始。PTN基因的外显子3和4与MK基因的外显子3和4关系最为密切，其中6个半胱氨酸残基编码于外显子3，4个半胱氨酸残基编码于外显子4，两个基因的内含子-外显子拼接通过相同的残基发生。这两个基因在编码高度碱性的C-末端结构域、翻译终止密码子和两个cDNA的多聚腺苷信号的第五外显子上的亲缘关系不那么密切。我们还报道了人胎盘中PTN基因5‘端非翻译序列的~2000个碱基和转录起始位置。用荧光原位杂交技术将PTN定位于人染色体7q33-34。这些数据证实了一个新的发育调节细胞因子基因家族的存在。控制胎儿生长和发育的分子事件目前是密集研究的主题。多碘营养素(PTN)(Milner等人，1989；Li等人，1990)、中期因子(MK)(Kadomatsu等人，1988；Tomomura等人，1990 a)和维甲酸诱导的肝素结合蛋白(RI-HB)(Vigny等人，1989；Raulais等人，1991；Urios等人，1991)是最近发现的一个发育调节细胞因子家族的成员，既显示神经营养特性，又显示有丝分裂原特性。RI-HB(可能是MK的禽类同源物)和MK都可以在mRNA和蛋白质水平上被维甲酸诱导(Kadomatsu等人，1988；Tomorura等人，1990b；Raulais等人，1991)。这些基因在胎儿发育过程中广泛表达(Li等人，1990；Kadomatsu等人，1990)，其蛋白产物与肝素结合，从而保持基底膜和细胞基质的联系。随着胎儿的快速生长和器官发生，这些细胞因子的分布模式显著减少。到了妊娠中期，MK基因只在肾脏表达(Kadomatsu等人，1990年)，因此被命名为中期因子或m/d妊娠小鼠Kiney基因，RI-Hb蛋白在新孵化的鸡中仅在晶状体囊和虹膜中表达(Vigny等人，)。PTN在出生时存在于大鼠的脑、肠、肌肉、皮肤、心脏、肺和肾脏中，出生后1个月似乎仅限于肠和脑(Li等人，1990；Merenmies&Rauvala，1990)。在成人中，PTN mRNA的表达只能在脑和子宫中检测到(Li等人，1990)，尽管最近从成人中克隆了PTN基因
Revised Manuscript Received September 11, 1992 abstract: Pleiotrophin (PTN), midkine (MK), and retinoic acid-induced heparin-binding (RI-HB) protein are members of a recently discovered family of developmentally regulated cytokines. We report here the cloning, sequencing, chromosomal localization, and structural organization of the genomic version of the human PTN gene and its comparison to the mouse MK gene. The PTN gene was found to be arranged in five exons and four introns, in a fashion similar to that of the mouse MK gene. Exon 1, as for MK, does not appear to encode amino acid sequence. As in the case of the MK gene, exon 2encodes the hydrophobic leader sequence of PTN, which constitutes the beginning of gene translation. The signal peptidecleavage site of both genes lies toward the 3'end of exon 2. Exons 3 and 4 of PTN were most closely related to exons 3 and 4 of the MK gene; in particular, six of the ten cysteine residues were coded for in exon 3 and the remaining 4 in exon 4. The intron-exon splice junctions of both genes occurred through the same residues. The two genes were found to be less closely related in the fifth exon which encodes the highly basic C-terminal domains, the translation termination codon, and the polyadenylation signal of both cDNAs. We also report~ 2000 bp of the 5'untranslated sequence of the PTN gene andthe site of initiation of transcriptionin human placenta. PTN was localized to human chromosome 7q33-34 by fluorescence in situ hybridization. These data confirm the existence of a new gene family of developmentally regulated cytokines.The molecular events which control fetal growth and development are currently the subject of intense investigation. Pleiotrophin (PTN)(Milner et al., 1989; Li et al., 1990), midkine (MK)(Kadomatsu et al., 1988; Tomomura et al., 1990a), and retinoic acid-induced heparin-binding (RI-HB) protein (Vigny et al., 1989; Raulais et al., 1991; Urios et al., 1991) are members of a recently discovered familyof developmentally regulated cytokines which display both neurotrophic and mitogenic properties. Both RI-HB (which may be the avian homologue of MK) and MK are inducible by retinoic acid at both the mRNA and protein level (Kadomatsu et al., 1988; Tomorura et al., 1990b; Raulais et al., 1991). These genes are widely expressed during devel-opment in thefetus (Li et al., 1990; Kadomatsu et al., 1990), and their protein products bind to heparin, thus remaining basement membrane and cell matrix associated. Following the period of rapid fetal growth and organogenesis, the pattern of distribution of these cytokines is dramatically reduced. By midgestation, MK mRNA was found to be expressed only in the kidney (Kadomatsu et al., 1990), hence the name midkine or m/dgestational mouse kiney gene, and RI-HB protein expression was restricted to the lens capsule and iris in newly hatched chickens (Vigny et al., 1989). PTN expression, which is present at birth inthe rat brain, intestine, muscle, skin, heart, lung, and kidney, appears 1 month postnatally to be limited to the intestine and brain (Li et al., 1990; Merenmies & Rauvala, 1990). In the adult, PTN mRNA expression could only be detected in the brain and uterus (Li et al., 1990), although PTN cDNA has recently been cloned from adult