The guanine nucleotide exchange factor ARNO mediates the activation of ARF and phospholipase D by insulin.
The guanine nucleotide exchange factor ARNO mediates the activation of ARF and phospholipase D by insulin.
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鸟嘌呤核苷酸交换因子Arno通过胰岛素介导了ARF和磷脂酶D的激活。
DOI：
10.1186/1471-2121-4-13
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发表时间：
2003-09-11
期刊：
影响因子：
--
通讯作者：
Romero G
中科院分区：
文献类型：
--
作者：
Li HS;Shome K;Rojas R;Rizzo MA;Vasudevan C;Fluharty E;Santy LC;Casanova JE;Romero G
Phospholipase D (PLD) is involved in many signaling pathways. In most systems, the activity of PLD is primarily regulated by the members of the ADP-Ribosylation Factor (ARF) family of GTPases, but the mechanism of activation of PLD and ARF by extracellular signals has not been fully established. Here we tested the hypothesis that ARF-guanine nucleotide exchange factors (ARF-GEFs) of the cytohesin/ARNO family mediate the activation of ARF and PLD by insulin. Wild type ARNO transiently transfected in HIRcB cells was translocated to the plasma membrane in an insulin-dependent manner and promoted the translocation of ARF to the membranes. ARNO mutants: ΔCC-ARNO and CC-ARNO were partially translocated to the membranes while ΔPH-ARNO and PH-ARNO could not be translocated to the membranes. Sec7 domain mutants of ARNO did not facilitate the ARF translocation. Overexpression of wild type ARNO significantly increased insulin-stimulated PLD activity, and mutations in the Sec7 and PH domains, or deletion of the PH or CC domains inhibited the effects of insulin. Small ARF-GEFs of the cytohesin/ARNO family mediate the activation of ARF and PLD by the insulin receptor. The online version of this article (doi:10.1186/1471-2121-4-13) contains supplementary material, which is available to authorized users.
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