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丝裂原活化蛋白激酶激酶1(MKK1)受苏氨酸磷酸化负调控。

Mitogen-activated protein kinase kinase 1 (MKK1) is negatively regulated by threonine phosphorylation.

作者信息

Rossomando A J, Dent P, Sturgill T W, Marshak D R

机构信息

W. M. Keck Structural Biology Laboratory, Beckman Neuroscience Center, Cold Spring Harbor Laboratory, New York 11724.

出版信息

Mol Cell Biol. 1994 Mar;14(3):1594-602. doi: 10.1128/mcb.14.3.1594-1602.1994.

DOI:10.1128/mcb.14.3.1594-1602.1994
PMID:8114697
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC358518/
Abstract

Mitogen-activated protein kinase kinase 1 (MKK1), a dual-specificity tyrosine/threonine protein kinase, has been shown to be phosphorylated and activated by the raf oncogene product as part of the mitogen-activated protein kinase cascade. Here we report the phosphorylation and inactivation of MKK1 by phosphorylation on threonine 286 and threonine 292. MKK1 contains a consensus phosphorylation site for p34cdc2, a serine/threonine protein kinase that regulates the cell division cycle, at Thr-286 and a related site at Thr-292. p34cdc2 catalyzes the in vitro phosphorylation of MKK1 on both of these threonine residues and inactivates MKK1 enzymatic activity. Both sites are phosphorylated in vivo as well. The data presented in this report provide evidence that MKK1 is negatively regulated by threonine phosphorylation.

摘要

丝裂原活化蛋白激酶激酶1(MKK1)是一种双特异性酪氨酸/苏氨酸蛋白激酶,已被证明作为丝裂原活化蛋白激酶级联反应的一部分,可被raf癌基因产物磷酸化并激活。在此,我们报告MKK1在苏氨酸286和苏氨酸292位点发生磷酸化后失活。MKK1在苏氨酸286位点含有一个p34cdc2(一种调节细胞分裂周期的丝氨酸/苏氨酸蛋白激酶)的共有磷酸化位点,在苏氨酸292位点有一个相关位点。p34cdc2在体外催化MKK1这两个苏氨酸残基的磷酸化反应,并使MKK1的酶活性失活。这两个位点在体内也会被磷酸化。本报告中的数据提供了证据,表明MKK1受到苏氨酸磷酸化的负调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad5/358518/948be5d00895/molcellb00003-0082-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad5/358518/2f09d9167ef5/molcellb00003-0078-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad5/358518/6e85eb71bf8d/molcellb00003-0078-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad5/358518/9a16c7d554c7/molcellb00003-0080-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad5/358518/77c10f2d1986/molcellb00003-0081-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad5/358518/663489b67e91/molcellb00003-0081-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad5/358518/4b4292a3b634/molcellb00003-0081-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad5/358518/948be5d00895/molcellb00003-0082-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad5/358518/2f09d9167ef5/molcellb00003-0078-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad5/358518/6e85eb71bf8d/molcellb00003-0078-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad5/358518/9a16c7d554c7/molcellb00003-0080-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad5/358518/77c10f2d1986/molcellb00003-0081-a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad5/358518/663489b67e91/molcellb00003-0081-b.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad5/358518/4b4292a3b634/molcellb00003-0081-c.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5ad5/358518/948be5d00895/molcellb00003-0082-a.jpg

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1
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2
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EMBO J. 1993 Feb;12(2):787-94. doi: 10.1002/j.1460-2075.1993.tb05713.x.
3
Functional expression of a MAP kinase kinase in COS cells and recognition by an anti-STE7/byr1 antibody.一种丝裂原活化蛋白激酶激酶在COS细胞中的功能表达及抗STE7/byr1抗体的识别
J Biol Chem. 2020 Mar 6;295(10):3000-3016. doi: 10.1074/jbc.RA119.012231. Epub 2020 Jan 29.
4
Integrin beta 4 (ITGB4) and its tyrosine-1510 phosphorylation promote pancreatic tumorigenesis and regulate the MEK1-ERK1/2 signaling pathway.整合素β 4(ITGB4)及其酪氨酸-1510 磷酸化促进胰腺肿瘤发生,并调节 MEK1-ERK1/2 信号通路。
Bosn J Basic Med Sci. 2020 Feb 5;20(1):106-116. doi: 10.17305/bjbms.2019.4255.
5
Mechanisms shaping the role of ERK1/2 in cellular senescence (Review).ERK1/2 在细胞衰老中的作用形成机制(综述)。
Mol Med Rep. 2019 Feb;19(2):759-770. doi: 10.3892/mmr.2018.9712. Epub 2018 Nov 29.
6
Negative feedback regulation of the ERK1/2 MAPK pathway.ERK1/2丝裂原活化蛋白激酶(MAPK)通路的负反馈调节
Cell Mol Life Sci. 2016 Dec;73(23):4397-4413. doi: 10.1007/s00018-016-2297-8. Epub 2016 Jun 24.
7
MicroRNA-Based Therapeutic Strategies for Targeting Mutant and Wild Type RAS in Cancer.基于微小RNA的癌症中靶向突变型和野生型RAS的治疗策略
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8
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J Biol Chem. 2015 Jun 26;290(26):16319-29. doi: 10.1074/jbc.M115.654897. Epub 2015 May 13.
9
MEK genomics in development and disease.MEK 基因组学在发育和疾病中的作用。
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10
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Cell Microbiol. 2011 Jun;13(6):836-45. doi: 10.1111/j.1462-5822.2011.01582.x. Epub 2011 Mar 4.
FEBS Lett. 1993 Feb 8;317(1-2):12-6. doi: 10.1016/0014-5793(93)81481-e.
4
Identification and characterization of a new mammalian mitogen-activated protein kinase kinase, MKK2.一种新的哺乳动物丝裂原活化蛋白激酶激酶MKK2的鉴定与特性分析
Mol Cell Biol. 1993 Aug;13(8):4539-48. doi: 10.1128/mcb.13.8.4539-4548.1993.
5
The growth factor-inducible immediate-early gene 3CH134 encodes a protein-tyrosine-phosphatase.生长因子诱导即刻早期基因3CH134编码一种蛋白酪氨酸磷酸酶。
Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5292-6. doi: 10.1073/pnas.90.11.5292.
6
MAP kinase-related FUS3 from S. cerevisiae is activated by STE7 in vitro.来自酿酒酵母的与丝裂原活化蛋白激酶相关的FUS3在体外被STE7激活。
Nature. 1993 Mar 18;362(6417):261-4. doi: 10.1038/362261a0.
7
Molecular structure of a protein-tyrosine/threonine kinase activating p42 mitogen-activated protein (MAP) kinase: MAP kinase kinase.一种激活p42丝裂原活化蛋白(MAP)激酶的蛋白酪氨酸/苏氨酸激酶的分子结构:MAP激酶激酶
Proc Natl Acad Sci U S A. 1993 Jan 1;90(1):173-7. doi: 10.1073/pnas.90.1.173.
8
cAMP antagonizes p21ras-directed activation of extracellular signal-regulated kinase 2 and phosphorylation of mSos nucleotide exchange factor.环磷酸腺苷(cAMP)拮抗p21ras介导的细胞外信号调节激酶2的激活以及mSos核苷酸交换因子的磷酸化。
EMBO J. 1993 Nov;12(11):4211-20. doi: 10.1002/j.1460-2075.1993.tb06105.x.
9
Inhibition by cAMP of Ras-dependent activation of Raf.环磷酸腺苷(cAMP)对Ras依赖性Raf激活的抑制作用。
Science. 1993 Nov 12;262(5136):1069-72. doi: 10.1126/science.7694367.
10
Inhibition of the EGF-activated MAP kinase signaling pathway by adenosine 3',5'-monophosphate.3',5'-单磷酸腺苷对表皮生长因子激活的丝裂原活化蛋白激酶信号通路的抑制作用
Science. 1993 Nov 12;262(5136):1065-9. doi: 10.1126/science.7694366.