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首页> 外文期刊>Cellular Signalling >RGS19 enhances cell proliferation through its C-terminal PDZ motif
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RGS19 enhances cell proliferation through its C-terminal PDZ motif

机译：RGS19通过其C端PDZ基序增强细胞增殖

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摘要

Regulator of G protein signaling 19 (RGS19), also known as Gα-interacting protein (GAIP), is a GTPase activating protein (GAP) for Gα_i subunits. Apart from its GAP function, RGS19 has been implicated in growth factor signaling through binding to GAIP-interacting protein C-terminus (GIPC) via its C-terminal PDZ-binding motif. To gain additional insight on its function, we have stably expressed RGS19 in a number of mammalian cell lines and examined its effect on cell proliferation. Interestingly, overexpression of RGS19 stimulated the growth of HEK293, PC12, Caco2, and NIH3T3 cells. This growth promoting effect was not shared by other RGS proteins including RGS4, RGS10 and RGS20. Despite its ability to stimulate cell proliferation, RGS19 failed to induce neoplastic transformation in NIH3T3 cells as determined by focus formation and soft-agar assays, and it did not induce tumor growth in athymic nude mice. Deletion mutants of RGS19 lacking the PDZ-binding motif failed to complex with GIPC and did not exhibit any growth promoting effect. Overexpression of GIPC alone in HEK293 cells stimulated cell proliferation whereas its knockdown in H1299 non-small cell lung carcinomas suppressed cell proliferation. This study demonstrates that RGS19, in addition to acting as a GAP, is able to stimulate cell proliferation in a GIPC-dependent manner.
机译：G蛋白信号传导19（RGS19）的调节剂，也称为Gα相互作用蛋白（GAIP），是Gα_1亚基的GTPase活化蛋白（GAP）。除了其GAP功能外，RGS19还通过其C端PDZ结合基序与GAIP相互作用蛋白C末端（GIPC）结合，参与了生长因子信号传导。为了获得对其功能的更多了解，我们已经在多种哺乳动物细胞系中稳定表达了RGS19，并研究了其对细胞增殖的影响。有趣的是，RGS19的过表达刺激了HEK293，PC12，Caco2和NIH3T3细胞的生长。其他RGS蛋白（包括RGS4，RGS10和RGS20）没有共享这种促进生长的作用。尽管它具有刺激细胞增殖的能力，但如通过病灶形成和软琼脂试验确定的那样，RGS19未能诱导NIH3T3细胞发生肿瘤转化，并且它也没有诱导无胸腺裸鼠中的肿瘤生长。缺少PDZ结合基序的RGS19的缺失突变体不能与GIPC复合并且没有表现出任何促进生长的作用。单独的GIPC在HEK293细胞中的过表达刺激细胞增殖，而在H1299非小细胞肺癌中的基因敲低则抑制细胞增殖。这项研究表明，RGS19除充当GAP外，还能够以GIPC依赖的方式刺激细胞增殖。

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