ISOLATION OF A SRC HOMOLOGY 2-CONTAINING TYROSINE PHOSPHATASE
ISOLATION OF A SRC HOMOLOGY 2-CONTAINING TYROSINE PHOSPHATASE
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DOI：
10.1073/pnas.89.3.1123
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发表时间：
1992-02-01
影响因子：
11.1
通讯作者：
ROSENBERG, RD
中科院分区：
文献类型：
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作者：
PLUTZKY, J;NEEL, BG;ROSENBERG, RD
酪氨酸磷酸化是由酪氨酸激酶和磷酸酪氨酸磷酸酶（PTP）的相反作用控制的。src同源2结构域（SH 2）存在于几种类型的信号蛋白中，包括一些酪氨酸激酶。这些结构域结合磷酸酪氨酸蛋白，从而有助于促进信号转导。使用混合的寡核苷酸定向聚合酶链反应，两个以前未描述的大鼠PTP cDNA片段产生。通过对大鼠巨核细胞和人红白血病细胞文库的筛选，我们获得了其中一个片段的全长编码序列。该cDNA SH-PTP 1编码含有两个高度保守的SH 2结构域的酪氨酸磷酸酶。SH-PTPI主要在造血细胞和上皮细胞中表达，具有2.4-腺苷酸酶nRNA、预测的595个氨基酸的开放阅读框和提示非跨膜蛋白的结构。当在大肠杆菌中表达时，SH-PTP 1具有PTP活性。SH-PTP 1的结构建立了酪氨酸磷酸酶家族的另一个分支，并提示酪氨酸磷酸酶可能参与信号转导途径的机制。
Tyrosine phosphorylation is controlled by the opposing actions of tyrosine kinases and phosphotyrosine phosphatases (PTPs). src homology 2 domains (SH2) are found in several types of signaling proteins, including some tyrosine kinases. These domains bind phosphotyrosyl proteins and thus help promote signal transduction. Using mixed oligonucleotide-directed polymerase chain reactions, two previously undescribed rat PTP cDNA fragments were generated. Through subsequent screening of rat megakaryocyte and human erythroleukemia libraries, we obtained a full-length coding sequence for one of these fragments. This cDNA, SH-PTP1, encodes a tyrosine phosphatase containing two highly conserved SH2 domains. SH-PTPI, with a 2.4-kilobase nRNA, a predicted open reading frame of 595 amino acids, and a structure suggesting a nontransmembrane protein, is expressed primarily in hematopoietic and epithelial cells. When expressed in Escherichia coli, SH-PTP1 possesses PTP activity. The structure of SH-PTP1 establishes an additional branch of the tyrosine phosphatase family and suggests mechanisms through which tyrosine phosphatases might participate in signal transduction pathways.