Plutzky J, Neel B G, Rosenberg R D
Department of Medicine, Brigham and Women's Hospital, Boston, MA 02118.
Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):1123-7. doi: 10.1073/pnas.89.3.1123.
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-PTP1, with a 2.4-kilobase mRNA, 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.
酪氨酸磷酸化受酪氨酸激酶和磷酸酪氨酸磷酸酶（PTPs）的相反作用控制。src同源2结构域（SH2）存在于多种信号蛋白中，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。利用混合寡核苷酸定向聚合酶链反应，产生了两个先前未描述的大鼠PTP cDNA片段。通过随后对大鼠巨核细胞和人红白血病文库的筛选，我们获得了其中一个片段的全长编码序列。这个cDNA，即SH-PTP1，编码一种含有两个高度保守的SH2结构域的酪氨酸磷酸酶。SH-PTP1具有2.4千碱基的mRNA，预测的开放阅读框为595个氨基酸，其结构表明它是一种非跨膜蛋白，主要在造血细胞和上皮细胞中表达。当在大肠杆菌中表达时，SH-PTP1具有PTP活性。SH-PTP1的结构建立了酪氨酸磷酸酶家族的一个额外分支，并提示了酪氨酸磷酸酶可能参与信号转导途径的机制。
