Expression and enzymatic activity of human disintegrin and metalloproteinase ADAM19/meltrin beta.

Expression and enzymatic activity of human disintegrin and metalloproteinase ADAM19/meltrin beta.
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DOI:
10.1006/bbrc.2000.4200
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发表时间:
2001-01
影响因子:
3.1
通讯作者:
Ping Wei;Yun-Ge Zhao;Zhuangwe Li;S. Ruben;Q. Sang
Ping Wei;Yun-Ge Zhao;Zhuangwe Li;S. Ruben;Q. Sang
中科院分区:
生物学4区
文献类型:
--
作者:
Ping Wei;Yun-Ge Zhao;Zhuangwe Li;S. Ruben;Q. Sang

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adamalysins参与蛋白水解、粘附、融合和细胞内信号传导。人ADAM 19/adamalysin-19(一种去整合素和金属蛋白酶19)从原代树突状细胞cDNA文库中鉴定。其具有信号序列、具有“半胱氨酸开关”残基的前结构域、具有锌结合位点的金属蛋白酶结构域、去整合素、富含半胱氨酸的结构域、表皮生长因子样结构域、跨膜结构域和具有推定的SH 3配体结合位点的胞质结构域。其mRNA在胎盘、心脏、膀胱、淋巴结和白细胞、结肠直肠腺癌SW 480和其他器官/细胞中表达。在人细胞中表达hADAM 19重组蛋白。它与α-2巨球蛋白(α 2-M)形成复合物并裂解。其蛋白水解活性被1,10-菲咯啉、EDTA、EGTA和合成的基质金属蛋白酶(MMP)抑制剂阻断,而不被金属蛋白酶TIMP-1和TIMP-2的组织抑制剂阻断。它不切割所测试的MMP底物,例如,I型胶原和明胶、酪蛋白和四种肽底物。因此,hADAM 19是一种活性金属蛋白酶,可能具有特定的底物谱。
The adamalysins are involved in proteolysis, adhesion, fusion, and intracellular signaling. Human ADAM19/adamalysin-19 (A disintegrin and metalloproteinase 19) was identified from primary dendritic cell cDNA libraries. It has a signal sequence, a pro-domain with a "cysteine-switch" residue, a metalloproteinase domain with a zinc-binding site, a disintegrin, a cysteine-rich domain, an epidermal-growth-factor-like domain, a transmembrane domain, and a cytoplasmic domain with putative SH3 ligand binding sites. Its mRNA was expressed in the placenta, heart, bladder, lymph nodes, and leukocytes, colorectal adenocarcinoma SW 480, and other organs/cells. The hADAM19 recombinant protein was expressed in human cells. It formed a complex with and cleaved alpha-2 macroglobulin (alpha2-M). Its proteolytic activity was blocked by 1,10-phenanthroline, EDTA, EGTA, and a synthetic matrix metalloproteinase (MMP) inhibitor and not by the tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2. It did not cleave the MMP substrates tested, e.g., type I collagen and gelatin, casein, and four peptide substrates. Thus, hADAM19 is an active metalloproteinase and may have a specific substrate profile.