Cloning of Seel-renewal factor receptors from hemopoietic stem cells

造血干细胞 Seel 更新因子受体的克隆

基本信息

批准号：
05454333
负责人：
SUDA Toshio
金额：
$ 4.35万
依托单位：
Kumamoto University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05454333/
关键词：
Hematopoietic Stem Cells Endothelial cells STK RON MSP TIE TEK Reccptor tyrosine kinases FACS TIE遺伝子 TEK遺伝子 RON遺伝子

项目摘要

Receptor and cytoplasmic tyrosine kinases essential functions in the hematopoietic cell development and signal transduction. In this project, we have characterized novel receptor tyrosine kinases, STK and TIE which are expresed in hematopoietic cells.STK encodes a 1,378 amino acid protein. STK was expressed in a various stage of hematopoietic cells including cells, but ont apparent expression in other adult tissues. We recently confirmed that STK prtein was phosphorylated by the binding of macrophage stimulating factor (MSP) of HGF-like protein (HLP) . As is the case in HGF/c-MET system, MSP/STK system is functional in hematopoietic cells. We have shown that MSP/STK play a role in the differentiation of macrophages and erythroid cells.TIE is unclassified RTK which is expressed in megakaryocytes and stem cells as well as endothelial cells. The amino acid homology between murine TIE and TEK was 46.2% in total. They shared a unique structural prperty of coexistent immunoglobulin-like domain, epidermal growth factor-like repeats, and fibronectin type lll repeats in their extracellular domains. The mouse TIE and TEK genes are located very close in chromosome4. This is syntenic to human chromosome region, 1p34 and 9p21, where the human TIE and TEK gene are mapped, respectively. Thus, TIE and TEK are tow linked members of a gene. Flow cytomery shows that TIE is mainly expressed in the fraction of CD34-positive of c-kit-positive cells. lt is interesting that TIE and TEK are expressed in both endothelial cells and hematopoietic stem cells, since both cells are thought to originate from the same progenitor cells. We hope that characterization of these kinases will be helpful to elucidate the molecular mechanism of the growth regulation of hematopoietic stem cells.

受体和细胞质酪氨酸激酶在造血细胞发育和信号转导中发挥重要作用。在这个项目中，我们鉴定了在造血细胞中表达的新型受体酪氨酸激酶 STK 和 TIE。STK 编码 1,378 个氨基酸的蛋白质。 STK在包括细胞在内的各个阶段的造血细胞中表达，但在其他成体组织中表达不明显。我们最近证实STK蛋白通过与HGF样蛋白(HLP)的巨噬细胞刺激因子(MSP)的结合而被磷酸化。与HGF/c-MET系统的情况一样，MSP/STK系统在造血细胞中发挥功能。我们已经证明MSP/STK在巨噬细胞和红系细胞的分化中发挥作用。TIE是未分类的RTK，在巨核细胞、干细胞以及内皮细胞中表达。小鼠TIE与TEK的氨基酸同源性总计为46.2%。它们在胞外域中具有共存的免疫球蛋白样结构域、表皮生长因子样重复序列和纤连蛋白III型重复序列的独特结构特性。小鼠 TIE 和 TEK 基因位于第 4 号染色体上非常接近。这与人类染色体区域 1p34 和 9p21 是同线性的，人类 TIE 和 TEK 基因分别位于此处。因此，TIE 和 TEK 是基因的两个连锁成员。流式细胞术显示TIE主要表达于c-kit阳性细胞中CD34阳性部分。有趣的是，TIE 和 TEK 在内皮细胞和造血干细胞中均表达，因为这两种细胞被认为源自相同的祖细胞。我们希望这些激酶的表征将有助于阐明造血干细胞生长调节的分子机制。