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GTP酶激活蛋白在通过磷脂酰胆碱水解磷脂酶C的促有丝分裂信号传导中的作用

Role of GTPase activating protein in mitogenic signalling through phosphatidylcholine-hydrolysing phospholipase C.

作者信息

Dominguez I, Marshall M S, Gibbs J B, García de Herreros A, Cornet M E, Graziani G, Diaz-Meco M T, Johansen T, McCormick F, Moscat J

机构信息

Medicina y Cirugía Experimental, Hospital General Gregorio Marañón, Madrid, Spain.

出版信息

EMBO J. 1991 Nov;10(11):3215-20. doi: 10.1002/j.1460-2075.1991.tb04884.x.

DOI:10.1002/j.1460-2075.1991.tb04884.x
PMID:1655413
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC453045/
Abstract

Recent evidence has accumulated showing that activation of PLC-catalysed hydrolysis of phosphatidylcholine (PC-PLC) is a critical step in mitogenic signal transduction both in fibroblasts and in oocytes from Xenopus laevis. The products of ras genes activate PC-PLC, bind guanine nucleotides, have intrinsic GTPase activity, and are regulated by a GTPase-activating protein (GAP). It has been suggested that, in addition to its regulatory properties, GAP may also be necessary for ras function as a downstream effector molecule. In this study, evidence is presented that strongly suggests that the functional interaction between ras p21 and GAP is sufficient and necessary for activation of maturation promoting factor (MPF) H1-kinase activity in oocytes, and that PC hydrolysis is critically involved in this mechanism. Therefore, we identify GAP as a further step required for signalling through PC-PLC, and necessary for the control of oocyte maturation in response to ras p21/insulin but not to progesterone.

摘要

最近积累的证据表明，磷脂酶C催化的磷脂酰胆碱水解（PC-PLC）的激活是成纤维细胞和非洲爪蟾卵母细胞有丝分裂信号转导中的关键步骤。ras基因的产物激活PC-PLC，结合鸟嘌呤核苷酸，具有内在的GTP酶活性，并受GTP酶激活蛋白（GAP）的调节。有人提出，除了其调节特性外，GAP对于ras作为下游效应分子发挥功能可能也是必需的。在本研究中，有证据强烈表明，ras p21与GAP之间的功能相互作用对于激活卵母细胞中的成熟促进因子（MPF）H1激酶活性是充分且必要的，并且PC水解在此机制中起关键作用。因此，我们确定GAP是通过PC-PLC进行信号传导所需的进一步步骤，并且是响应ras p21/胰岛素而非孕酮控制卵母细胞成熟所必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5913/453045/6fa5e6a26384/emboj00109-0097-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5913/453045/72a5e16df5b4/emboj00109-0095-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5913/453045/77b9be423205/emboj00109-0095-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5913/453045/6fa5e6a26384/emboj00109-0097-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5913/453045/72a5e16df5b4/emboj00109-0095-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5913/453045/77b9be423205/emboj00109-0095-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5913/453045/6fa5e6a26384/emboj00109-0097-a.jpg

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