DEVELOPMENTAL EXPRESSION OF 4 NOVEL SERINE THREONINE KINASE RECEPTORS HOMOLOGOUS TO THE ACTIVIN TRANSFORMING GROWTH-FACTOR-BETA TYPE-II RECEPTOR FAMILY

DEVELOPMENTAL EXPRESSION OF 4 NOVEL SERINE THREONINE KINASE RECEPTORS HOMOLOGOUS TO THE ACTIVIN TRANSFORMING GROWTH-FACTOR-BETA TYPE-II RECEPTOR FAMILY
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DOI:
10.1002/aja.1001960207
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发表时间:
1993-02-01
影响因子:
2.5
通讯作者:
DONAHOE, PK
DONAHOE, PK
中科院分区:
生物学3区
文献类型:
--
作者:
HE, WW;GUSTAFSON, ML;DONAHOE, PK

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丝氨酸/苏氨酸激酶跨膜蛋白是一个新的生长因子信号转导蛋白家族,包括活化素II型受体和转化生长因子β的II型受体的几种亚型。为了克隆苗勒管抑制物质受体(转化生长因子β超家族的成员),从这些受体激酶结构域的保守区域设计寡核苷酸引物,用于PCR扩增胎鼠泌尿生殖嵴cDNA。我们以这种方式分离出四种新的受体(命名为R1-R4),每种受体都具有以前克隆的激酶的结构特征,包括一个小的胞外配体结合结构域,一个单一的疏水跨膜结构域和一个胞内丝氨酸/苏氨酸激酶结构域。此外,每个都有特征性的激酶亚结构域和保守的丝氨酸/苏氨酸激酶序列在这个家庭中发现。北方分析显示,R1-R4的mRNA表达在几个组织,包括胎儿泌尿生殖嵴,睾丸,卵巢,以及脑和肺。原位杂交进一步将R1定位于14.5至15天胎鼠苗勒管的间充质和窦前和窦卵泡的卵母细胞,这些位点与苗勒管抑制物质受体的预测定位一致。此外,R2专门定位于生精后睾丸的曲细精管。这些激活素和转化生长因子-β II型受体家族的最新成员应该有助于定义该配体超家族通过膜磷酸化影响细胞生长和分化的分子机制。(C)1993 Wiley-Liss,Inc.
Serine/threonine kinase transmembrane proteins are a new family of growth factor signal transducers that includes several isoforms of the activin type II receptor and the type II receptor for transforming growth factor-beta. In an effort to clone the receptor for Mullerian inhibiting substance, a member of the transforming growth factor-beta superfamily, oligonucleotide primers designed from conserved regions of these receptors' kinase domains were used for PCR amplification of fetal rat urogenital ridge cDNA. We isolated four novel receptors in this manner (designated R1-R4), each of which has structural features of the previously cloned kinases, including a small extracellular ligand-binding domain, a single hydrophobic transmembrane domain, and an intracellular serine/threonine kinase domain. In addition, each has characteristic kinase subdomains and conserved serine/threonine kinase sequences found in this family. Northern analysis revealed mRNA expression of R1-R4 in several tissues, including fetal urogenital ridge, testis, and ovary, as well as brain and lung. In situ hybridization further localized R1 to mesenchyme of the 14.5 to 15-day fetal rat Mullerian duct and to oocytes of preantral and antral follicles, sites that are consistent with the predicted localization of Mullerian inhibiting substance receptor. In addition, R2 localized specifically to seminiferous tubules of the postnatal testis. These newest members of the activin and transforming growth factor-beta type II receptor family should help define the molecular mechanisms by which this ligand superfamily affects cell growth and differentiation via membrane phosphorylation. (C) 1993 Wiley-Liss, Inc.