SEQUENCE OF MET PROTOONCOGENE CDNA HAS FEATURES CHARACTERISTIC OF THE TYROSINE KINASE FAMILY OF GROWTH-FACTOR RECEPTORS

SEQUENCE OF MET PROTOONCOGENE CDNA HAS FEATURES CHARACTERISTIC OF THE TYROSINE KINASE FAMILY OF GROWTH-FACTOR RECEPTORS
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DOI:
10.1073/pnas.84.18.6379
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发表时间:
1987-09-01
影响因子:
11.1
通讯作者:
VANDEWOUDE, G
VANDEWOUDE, G
中科院分区:
综合性期刊1区
文献类型:
--
作者:
PARK, M;DEAN, M;VANDEWOUDE, G

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我们分离了与主要 MET 原癌基因转录物相对应的重叠 cDNA 克隆。 cDNA 核苷酸序列包含 1408 个氨基酸的开放阅读框,具有生长因子受体酪氨酸激酶家族的特征。这些特征包括假定的 24 个氨基酸信号肽和候选的 23 个氨基酸的疏水性跨膜片段,该片段定义了 926 个氨基酸的胞外结构域,可用作配体结合结构域。推定的 435 个氨基酸长的胞内结构域与酪氨酸激酶 SRC 家族具有高度同源性,并且激酶结构域内与人胰岛素受体 (44%) 和 v-abl (41%) 的同源性最高。然而,尽管有这些相似之处,我们在推定的配体结合域中没有发现与其他生长因子受体的明显序列同源性。我们从这些结果中得出结论,MET 原癌基因是一种尚未知配体的细胞表面受体。
We isolated overlapping cDNA clones corresponding to the major MET protooncogene transcript. The cDNA nucleotide sequence contained an open reading frame of 1408 amino acids with features characteristic of the tyrosine kinase family of growth factor receptors. These features include a putative 24-amino acid signal peptide and a candidate, hybrophobic, membrane-spanning segment of 23 amino acids, which defines an extracellular domain of 926 amino acids that could serve as a ligand-binding domain. A putative intracellular domain 435 amino acids long shows high homology with the SRC family of tyrosine kinases and within the kinase domain is most homologous with the human insulin receptor (44%) and v-abl (41%). Despite these similarities, however, we found no apparent sequence homology to other growth factor receptors in the putative ligand-binding domain. We conclude from these results that the MET protooncogene is a cell-surface receptor for an as-yet-unknown ligand.