Kometani Kohei, Ishida Daisuke, Hattori Masakazu, Minato Nagahiro
Department of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606-8501, Japan.
Trends Mol Med. 2004 Aug;10(8):401-8. doi: 10.1016/j.molmed.2004.06.004.
Rap1 is a member of the Ras family of GTPases and, depending on the cellular context, has an important role in the regulation of proliferation or cell adhesion. In lymphohematopoietic tissues, SPA-1 is a principal Rap1 GTPase-activating protein. Mice that are deficient for the SPA-1 gene develop age-dependent progression of T-cell immunodeficiency followed by a spectrum of late onset myeloproliferative disorders, mimicking human chronic myeloid leukemia. Recent studies reveal that deregulated Rap1 activation in SPA-1-deficient mice causes enhanced expansion of the bone marrow hematopoietic progenitors, but induces progressive unresponsiveness or anergy in T cells. Rap1 and its regulator, SPA-1, could, therefore, provide unique molecular targets for the control of human hematologic malignancy.
Rap1是GTP酶Ras家族的成员之一，根据细胞环境的不同，在增殖调节或细胞黏附中发挥重要作用。在淋巴造血组织中，SPA-1是主要的Rap1 GTP酶激活蛋白。SPA-1基因缺陷的小鼠会出现年龄依赖性的T细胞免疫缺陷进展，随后出现一系列迟发性骨髓增殖性疾病，类似于人类慢性髓性白血病。最近的研究表明，SPA-1缺陷小鼠中Rap1激活失调会导致骨髓造血祖细胞的扩增增强，但会诱导T细胞逐渐无反应或无能。因此，Rap1及其调节因子SPA-1可能为控制人类血液系统恶性肿瘤提供独特的分子靶点。
