Human SPA-1 gene product selectively expressed in lymphoid tissues is a specific GTPase-activating protein for Rap1 and Rap2 - Segregate expression profiles from a rap1GAP gene product
Human SPA-1 gene product selectively expressed in lymphoid tissues is a specific GTPase-activating protein for Rap1 and Rap2 - Segregate expression profiles from a rap1GAP gene product
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DOI：
10.1074/jbc.272.44.28081
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发表时间：
1997-10-31
影响因子：
4.8
通讯作者：
Minato, N
中科院分区：
文献类型：
--
作者：
Kurachi, H;Wada, Y;Minato, N
在有丝分裂刺激下，具有与人rap1GAP基因同源区域的小鼠Spa-1基因在淋巴细胞中被转录诱导，本文克隆了人类Spa-1基因的cDNA。SPA-1 cDNA编码一个130 kda的蛋白（p130(SPA-1)），由富含脯氨酸的区域和rap1gap相关结构域组成，然后是一个卷曲的线圈拉伸。杆状病毒表达的p130（SPA-1）对Rap1和Rap2表现出gtpase激活蛋白（GAP）活性，但对Ras、Rho、Cdc42、Pac和Ran没有活性，其特异性活性与rap1GAP基因产物（p85/95(rap1GAP)）相当。在细胞中，p130（SPA-1）多定位于与Rap1和Rap2共定位的核周膜区，在各种组织中，SPA-1和rap1GAP基因的表达倾向于分离，淋巴组织中表达丰富的SPA-1转录物而不表达rap1GAP，而在脑、肾、胰腺等组织中表达rap1GAP mRNA而很少表达SPA-1，早幼粒细胞HL-60细胞中表达p130（SPA-1）而很少表达p85/95(rap1GAP)，处于未诱导状态。p130（SPA-1）逐渐下降，p85/95（rap1GAP）相反急剧增加，因为它们停止增殖并被12- o - tetradecanoylphorbol13 -acetate分化为巨噬细胞。这些结果表明，尽管Rap1和Rap2的GAP活性相当，但SPA-1和rap1GAP基因的产物在不同的环境下发挥作用，这取决于细胞类型和/或状态。
Mouse Spa-1 gene with a region homologous to the human rap1GAP gene is transcriptionally induced in the lymphocytes by mitogenic stimulation, Herein we have cloned a cDNA for its human counterpart. SPA-1 cDNA encodes a 130-kDa protein (p130(SPA-1)) consisting of proline-rich regions and rap1GAP-related domain followed by a coiled coil stretch. Baculovirally expressed p130(SPA-1) exhibited GTPase-activating protein (GAP) activity for Rap1 and Rap2, but not for Ras, Rho, Cdc42, Pac, and Ran, with comparable specific activity to the rap1GAP gene product (p85/95(rap1GAP)). In the cells, p130(SPA-1) was mostly localized at the perinuclear membranous region co-localizing with Rap1 and Rap2, Expression of SPA-1 and rap1GAP genes tended to be segregate in various tissues, lymphoid tissues expressing abundant SPA-1 transcript without rap1GAP, while those such as brain, kidney, and pancreas exhibiting rap1GAP mRNA with little SPA-1, Promyelocytic HL-60 cells, which expressed p130(SPA-1) With little p85/95(rap1GAP) in uninduced state, showed progressive decline in p130(SPA-1) and conversely drastic increase in p85/95(rap1GAP) as they ceased from proliferation and differentiated into macrophages by 12-O-tetradecanoylphorbol-13-acetate. These results suggested that products of SPA-1 and rap1GAP genes, albeit comparable GAP activity for Rap1 and Rap2, functioned in the distinct contexts depending on cell types and/or states.