A FAMILY OF RECEPTOR-LINKED PROTEIN TYROSINE PHOSPHATASES IN HUMANS AND DROSOPHILA

A FAMILY OF RECEPTOR-LINKED PROTEIN TYROSINE PHOSPHATASES IN HUMANS AND DROSOPHILA
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DOI:
10.1073/pnas.86.22.8698
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发表时间:
1989-11-01
影响因子:
11.1
通讯作者:
SAITO, H
SAITO, H
中科院分区:
综合性期刊1区
文献类型:
--
作者:
STREULI, M;KRUEGER, NX;SAITO, H

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为了了解酪氨酸磷酸化对细胞增殖的调节,蛋白酪氨酸磷酸酶(PTPase;蛋白酪氨酸磷酸磷酸水解酶,EC 3.1.3.48)的表征至关重要。人类基因 LCA(白细胞共同抗原)和 LAR 编码推定的受体相关 PTPase。通过使用共有序列探针,从果蝇中分离出另外两个受体连接的 PTPase 基因 DLAR 和 DPTP。 DLAR 和 DPTP 的胞外片段均由多个免疫球蛋白样结构域和 III 型纤连蛋白样结构域组成。 DLAR 和 DPTP 以及人 LCA 和 LAR 的细胞质区域由两个串联重复的 PTPase 结构域组成。通过测量 32P 标记的 [Tyr(P)] 肽中磷酸盐的释放来证明免疫沉淀的 LCA 和 LAR 的 PTPase 活性。此外,大肠杆菌中表达的 LCA、LAR、DLAR 和 DPTP 的胞质结构域具有 PTPase 活性。定点诱变表明保守的半胱氨酸残基对于 PTPase 活性至关重要。
To understand the regulation of cell proliferation by tyrosine phosphorylation, characterization of protein tyrosine phosphatases (PTPase; protein-tyrosine-phosphate phosphohydrolase, EC 3.1.3.48) is essential. The human genes LCA (leukocyte common antigen) and LAR encode putative receptor-linked PTPases. By using consensus sequence probes, two additional receptor-linked PTPase genes, DLAR and DPTP, were isolated from Drosophila melanogaster. The extracellular segments of both DLAR and DPTP are composed of multiple immunoglobulin-like domains and fibronectin type III-like domains. The cytoplasmic region of DLAR and DPTP, as well as human LCA and LAR, are composed of two tandemly repeated PTPase domains. PTPase activities of immunoprecipitated LCA and LAR were demonstrated by measuring the release of phosphate from a 32P-labeled [Tyr(P)]peptide. Furthermore, the cytoplasmic domains of LCA, LAR, DLAR, and DPTP, expressed in Escherichia coil, have PTPase activity. Site-directed mutagenesis showed that a conserved cysteine residue is essential for PTPase activity.