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Site-directed mutagenesis of nm23-H1. Mutation of proline 96 or serine 120 abrogates its motility inhibitory activity upon transfection into human breast carcinoma cells.nm23-H1的定点诱变。脯氨酸96或丝氨酸120发生突变后,转染到人乳腺癌细胞中时其运动抑制活性丧失。
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8
Nm23-H1 metastasis suppressor phosphorylation of kinase suppressor of Ras via a histidine protein kinase pathway.Nm23-H1 通过组氨酸蛋白激酶途径对Ras激酶抑制因子进行磷酸化。
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J Biol Chem. 2000 Nov 10;275(45):35570-6. doi: 10.1074/jbc.M006106200.
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Expression of a catalytically inactive H118Y mutant of nm23-H2 suppresses the metastatic potential of line IV Cl 1 human melanoma cells.nm23-H2的催化失活H118Y突变体的表达抑制了IV Cl 1人黑色素瘤细胞系的转移潜能。
Int J Cancer. 2000 Nov 15;88(4):547-53. doi: 10.1002/1097-0215(20001115)88:4<547::aid-ijc5>3.0.co;2-l.

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本文引用的文献

1
Site-directed mutation of Nm23-H1. Mutations lacking motility suppressive capacity upon transfection are deficient in histidine-dependent protein phosphotransferase pathways in vitro.Nm23-H1的定点突变。转染后缺乏运动抑制能力的突变体在体外组氨酸依赖性蛋白磷酸转移酶途径中存在缺陷。
J Biol Chem. 1997 Feb 28;272(9):5525-32. doi: 10.1074/jbc.272.9.5525.
2
The Enzymatic Activity of Drosophila AWD/NDP Kinase Is Necessary but Not Sufficient for Its Biological Function.果蝇AWD/NDP激酶的酶活性对其生物学功能而言是必要的,但并非充分条件。
Dev Biol. 1996 Aug 1;177(2):544-57.
3
Site-directed mutagenesis of nm23-H1. Mutation of proline 96 or serine 120 abrogates its motility inhibitory activity upon transfection into human breast carcinoma cells.nm23-H1的定点诱变。脯氨酸96或丝氨酸120发生突变后,转染到人乳腺癌细胞中时其运动抑制活性丧失。
J Biol Chem. 1996 Oct 11;271(41):25107-16. doi: 10.1074/jbc.271.41.25107.
4
Yeast HOG1 MAP kinase cascade is regulated by a multistep phosphorelay mechanism in the SLN1-YPD1-SSK1 "two-component" osmosensor.酵母HOG1丝裂原活化蛋白激酶级联反应由SLN1-YPD1-SSK1“双组分”渗透感受器中的多步磷酸化中继机制调控。
Cell. 1996 Sep 20;86(6):865-75. doi: 10.1016/s0092-8674(00)80162-2.
5
Decreased expression of nucleoside diphosphate kinase alpha isoform, an nm23-H2 gene homolog, is associated with metastatic potential of rat mammary-adenocarcinoma cells.核苷二磷酸激酶α亚型(一种nm23-H2基因同源物)表达降低与大鼠乳腺腺癌细胞的转移潜能相关。
Int J Cancer. 1996 Feb 8;65(4):531-7. doi: 10.1002/(SICI)1097-0215(19960208)65:4<531::AID-IJC23>3.0.CO;2-B.
6
A novel serine/threonine-specific protein phosphotransferase activity of Nm23/nucleoside-diphosphate kinase.Nm23/核苷二磷酸激酶的一种新型丝氨酸/苏氨酸特异性蛋白磷酸转移酶活性。
Eur J Biochem. 1995 Nov 15;234(1):200-7. doi: 10.1111/j.1432-1033.1995.200_c.x.
7
Inhibition of cell motility after nm23 transfection of human and murine tumor cells.人源和鼠源肿瘤细胞转染nm23后细胞运动性的抑制
Cancer Res. 1993 May 1;53(9):1971-3.
8
Transfection of human nm23-H1 into the human MDA-MB-435 breast carcinoma cell line: effects on tumor metastatic potential, colonization and enzymatic activity.将人nm23-H1转染到人MDA-MB-435乳腺癌细胞系:对肿瘤转移潜能、定植及酶活性的影响。
Oncogene. 1993 Sep;8(9):2325-33.
9
Drosophila awdK-pn, a homologue of the metastasis suppressor gene nm23, suppresses the Tum-1 haematopoietic oncogene.果蝇awdK-pn是转移抑制基因nm23的同源物,可抑制Tum-1造血癌基因。
Nat Genet. 1993 Jun;4(2):195-201. doi: 10.1038/ng0693-195.
10
A serine phosphorylation of Nm23, and not its nucleoside diphosphate kinase activity, correlates with suppression of tumor metastatic potential.Nm23的丝氨酸磷酸化而非其二磷酸核苷激酶活性与肿瘤转移潜能的抑制相关。
J Biol Chem. 1993 Dec 5;268(34):25780-9.

nm23的双组分激酶样活性与其运动抑制活性相关。

Two-component kinase-like activity of nm23 correlates with its motility-suppressing activity.

作者信息

Wagner P D, Steeg P S, Vu N D

机构信息

Laboratory of Biochemistry, Division of Basic Sciences, National Cancer Institute, Bethesda, MD 20892, USA.

出版信息

Proc Natl Acad Sci U S A. 1997 Aug 19;94(17):9000-5. doi: 10.1073/pnas.94.17.9000.

DOI:10.1073/pnas.94.17.9000
PMID:9256424
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC22999/
Abstract

Nm23 genes, which encode nucleoside diphosphate kinases, have been implicated in suppressing tumor metastasis. The motility of human breast carcinoma cells can be suppressed by transfection with wild-type nm23-H1, but not by transfections with two nm23-H1 mutants, nm23-H1(S12OG) and nm23-H1(P96S). Here we report that nm23-H1 can transfer a phosphate from its catalytic histidine to aspartate or glutamate residues on 43-kDa membrane proteins. One of the 43-kDa membrane proteins was not phosphorylated by either nm23-H1(P96S) or nm23-H1(S120G), and another was phosphorylated much more slowly by nm23-H1(P96S) and by nm23-H1(S120G) than by wild-type nm23-H1. Nm23-H1 also can transfer phosphate from its catalytic histidine to histidines on ATP-citrate lyase and succinic thiokinase. The rates of phosphorylation of ATP-citrate lyase by nm23-H1(S120G) and nm23-H1(P96S) were similar to that by wild-type nm23-H1. The rate of phosphorylation of succinic thiokinase by nm23-H1(S120) was similar to that by wild-type nm23-H1, and the rate of phosphorylation of succinic thiokinase by nm23-H1(P96S) was about half that by wild-type nm23-H1. Thus, the transfer of phosphate from nm23-H1 to aspartates or glutamates on other proteins appears to correlate better with the suppression of motility than does the transfer to histidines.

摘要

Nm23基因编码核苷二磷酸激酶,与抑制肿瘤转移有关。野生型nm23-H1转染可抑制人乳腺癌细胞的运动性,但两种nm23-H1突变体nm23-H1(S12OG)和nm23-H1(P96S)转染则无此作用。我们在此报告,nm23-H1可将其催化组氨酸上的磷酸基团转移至43 kDa膜蛋白的天冬氨酸或谷氨酸残基上。43 kDa膜蛋白中的一种既不被nm23-H1(P96S)也不被nm23-H1(S120G)磷酸化,另一种被nm23-H1(P96S)和nm23-H1(S120G)磷酸化的速度比被野生型nm23-H1磷酸化的速度慢得多。Nm23-H1还可将其催化组氨酸上的磷酸基团转移至ATP-柠檬酸裂解酶和琥珀酸硫激酶的组氨酸上。nm23-H1(S120G)和nm23-H1(P96S)对ATP-柠檬酸裂解酶的磷酸化速率与野生型nm23-H1相似。nm23-H1(S120)对琥珀酸硫激酶的磷酸化速率与野生型nm23-H1相似,而nm23-H1(P96S)对琥珀酸硫激酶的磷酸化速率约为野生型nm23-H1的一半。因此,nm23-H1将磷酸基团转移至其他蛋白的天冬氨酸或谷氨酸上似乎比转移至组氨酸上与运动性抑制的相关性更好。