A NOVEL ENDOTHELIAL-CELL SURFACE-RECEPTOR TYROSINE KINASE WITH EXTRACELLULAR EPIDERMAL GROWTH-FACTOR HOMOLOGY DOMAINS
A NOVEL ENDOTHELIAL-CELL SURFACE-RECEPTOR TYROSINE KINASE WITH EXTRACELLULAR EPIDERMAL GROWTH-FACTOR HOMOLOGY DOMAINS
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DOI：
10.1128/mcb.12.4.1698
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发表时间：
1992-04-01
影响因子：
5.3
通讯作者：
ALITALO, K
中科院分区：
文献类型：
--
作者：
PARTANEN, J;ARMSTRONG, E;ALITALO, K
内皮细胞表面在几个重要的生理和病理过程中发挥关键作用，如血液凝固，血管生成反应和炎症。在这里，我们描述的TIE，一种新型的人内皮细胞表面受体酪氨酸激酶的克隆和表征。预测的结蛋白产物的胞外结构域具有异常的多结构域结构，其由嵌入在两个免疫球蛋白样环之间的三个表皮生长因子同源基序的簇组成，所述免疫球蛋白样环之后是紧挨着跨膜区的三个纤连蛋白III型重复。此外，一个cDNA形式缺乏的三个表皮生长因子同源结构域的第一个被分离出来，这表明选择性剪接产生不同的领带型受体。用tie cDNA表达载体转染的细胞产生117 kDa的糖基化多肽，其与针对tie羧基末端产生的抗血清反应。Tie基因位于染色体1 p33 ~ 1 p34区域。Tie基因的表达似乎在某些细胞系中受到限制;在内皮细胞系和一些具有红细胞和巨核细胞特征的髓系白血病细胞系中检测到大量Tie mRNA。此外，mRNA原位研究进一步表明了Tie基因的内皮表达。Tie受体酪氨酸激酶可能已经进化为多种蛋白质-蛋白质相互作用，可能包括细胞粘附到血管内皮。
Endothelial cell surfaces play key roles in several important physiological and pathological processes such as blood clotting, angiogenic responses, and inflammation. Here we describe the cloning and characterization of tie, a novel type of human endothelial cell surface receptor tyrosine kinase. The extracellular domain of the predicted tie protein product has an exceptional multidomain structure consisting of a cluster of three epidermal growth factor homology motifs embedded between two immunoglobulinlike loops, which are followed by three fibronectin type III repeats next to the transmembrane region. Additionally, a cDNA form lacking the first of the three epidermal growth factor homology domains was isolated, suggesting that alternative splicing creates different tie-type receptors. Cells transfected with tie cDNA expression vector produce glycosylated polypeptides of 117 kDa which are reactive to antisera raised against the tie carboxy terminus. The tie gene was located in chromosomal region 1p33 to 1p34. Expression of the tie gene appeared to be restricted in some cell lines; large amounts of tie mRNA were detected in endothelial cell lines and in some myeloid leukemia cell lines with erythroid and megakaryoblastoid characteristics. In addition, mRNA in situ studies further indicated the endothelial expression of the tie gene. The tie receptor tyrosine kinase may have evolved for multiple protein-protein interactions, possibly including cell adhesion to the vascular endothelium.