Significance and functional analysis of protein-tyrosine phosphatases expressed in hematopoietic disorders.

已知蛋白酪氨酸磷酸酶（PTPs）在去除磷酸酪氨酸中的磷酸基团中起作用，磷酸酪氨酸在酪氨酸激酶激活后积累。我们已经分离出在造血细胞中表达的编码PTPs的cdna。在这里，我们研究了它们的基因组结构和表达的异常，以了解ptp与肿瘤发生的相关性。我们得到了如下所述的结果。我们分离了LC-PTP基因组克隆并证明了其基因组组织。LC-PTP基因由11个外显子组成，其组织结构与CD45基因（跨膜PTP）相似。通过本研究，我们可以用PCR方法分析LC-PTP基因的体细胞突变。我们发现LC-PTP基因在IL-2刺激下表达，并证明LC-PTP基因是一个早期反应基因。这一数据表明LC-PTP可以在t细胞增殖中发挥作用。我们绘制了SH-PTP基因图谱。SH-PTP基因位于染色体12q24.1，已知该位点与慢性淋巴细胞白血病（CLL）、生殖细胞肿瘤和平滑肌瘤的染色体异常有关。SH-PTP2在这些疾病中的功能分析值得关注。我们制备了SH-PTP2多克隆抗体，并观察了SHPTP2表达的定位。我们发现SHPTP2在血管平滑肌细胞中普遍高表达。我们正在研究SHPTP2在心血管系统中的功能。

Protein-tyrosine phosphatases (PTPs) are known to play a role in removal of phosphate groups from phosphotyrosines, which accumulate after activation of tyrosine kinases. We have already isolated cDNAs encoding PTPs expressed in hematopoietic cells. Here, we investigate the abnormalities of their genomic structures and expressions to see the correlation of PTPs with oncogenesis. We obtained the results as described below.We isolated LC-PTP genomic clones and demonstrated the genomic organization. LC-PTP gene consists of 11 exons and its organizations are similar to CD45 gene (transmembrane PTP). From this study, we can analyze the somatic mutations in LC-PTP gene by PCR method.We found LC-PTP gene expression is induced by IL-2 stimulation, and demonstrated that LC-PTP gene is an early response gene. This data suggests that LC-PTP can function in T-cell proliferation.We have mapped SH-PTP gene. SH-PTP gene is localized at chromosome 12q24.1 This locus is knowm to be associated with chromosomal abnormalities in chronic lymphocytic leukemia (CLL), germ cell tumors, and leiomyoma. It is of interest that functional analyzes of SH-PTP2 in the disorders.We generated polyclonal antibody to SH-PTP2, and see localization of SHPTP2 expressions. We found SHPTP2 is highly expressed in vascular smooth muscle cells ubiquitously. We are investigating SHPTP2 functions in cardiovascular system.