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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2019/05/30 11:36:55」(JST)

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Mitogen-activated protein kinase kinase (also known as MAP2K, MEK, MAPKK) is a kinase enzyme which phosphorylates mitogen-activated protein kinase (MAPK).

MAP2K is classified as EC 2.7.12.2.

There are seven genes:

MAP2K1 (a.k.a. MEK1)
MAP2K2 (a.k.a. MEK2)
MAP2K3 (a.k.a. MKK3)
MAP2K4 (a.k.a. MKK4)
MAP2K5 (a.k.a. MKK5)
MAP2K6 (a.k.a. MKK6)
MAP2K7 (a.k.a. MKK7)

The activators of p38 (MKK3 and MKK6), JNK (MKK4 and MKK7), and ERK (MEK1 and MEK2) define independent MAP kinase signal transduction pathways.^[1] The acronym MEK derives from MAPK/ERK Kinase.^[2]

Role in melanoma

MEK is a member of the MAPK signaling cascade that is activated in melanoma.^[3] When MEK is inhibited, cell proliferation is blocked and apoptosis(controlled cell death) is induced.

References

^ Dérijard B, et al. (1995). "Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms". Science. 267 (5198): 682–5. doi:10.1126/science.7839144. PMID 7839144.
^ Dwivedi, Gaurav; Kemp, Melissa L. (February 15, 2012). "Systemic Redox Regulation of Cellular Information Processing". Antioxidants & Redox Signaling. 16: 374–80. doi:10.1089/ars.2011.4034. PMC 3279717. PMID 21939387.
^ Falchook, Gerald S.; Lewis, Karl D.; Infante, Jeffrey R.; Gordon, Michael S.; Vogelzang, Nicholas J.; DeMarini, Douglas J.; Fecher, Leslie A.; et al. (2012). "Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial". The Lancet Oncology. 13 (8): 782–789. doi:10.1016/S1470-2045(12)70269-3. PMC 4109286. PMID 22805292.

External links

Mitogen-Activated+Protein+Kinase+Kinases at the US National Library of Medicine Medical Subject Headings (MeSH)

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3. 黒色腫（メラノーマ）の分子生物学 the molecular biology of melanoma
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English Journal

JNK Inhibition Reduced Retinal Ganglion Cell Death after Ischemia/Reperfusion In Vivo and after Hypoxia In Vitro.

Produit-Zengaffinen N1, Favez T2, Pournaras CJ3, Schorderet DF4,5,6.
Advances in experimental medicine and biology.Adv Exp Med Biol.2016;854:677-83. doi: 10.1007/978-3-319-17121-0_90.
Mitogen-activated protein kinases (MAPKs) are key regulators that have been linked to cell survival and death. Among the main classes of MAPKs, c-jun N-terminal kinase (JNK) has been shown to mediate cell stress responses associated with apoptosis. In Vitro, hypoxia induced a significant increase in
PMID 26427475

Sepsis protects the myocardium and other organs from subsequent ischaemic/reperfusion injury via a MAPK-dependent mechanism.

Walshe CM1, Laffey JG, Kevin L, O'Toole D.
Intensive care medicine experimental.Intensive Care Med Exp.2015 Dec;3(1):35. doi: 10.1186/s40635-014-0035-9. Epub 2015 Jan 31.
BACKGROUND: Sepsis has been shown to precondition the intact heart against ischaemia/reperfusion (IR) injury, and prior endotoxin exposure of cells in in vitro models has shown evidence of protection against subsequent simulated ischaemia. Our aim in this study is to validate these findings and furt
PMID 26215802

Japanese Journal

36.トマトACC合成酵素LeACS2の安定化には2ヵ所のリン酸化部位が必要である(口頭発表)

上吉原裕亮,森仁志
植物化学調節学会研究発表記録集 (45), 53, 2010-10-01
… CDPK inhibitor, calmidazolium, and MAPKK inhibitor, U0126, were decreased the amounts of phosphorylated form and total ACS protein. …
NAID 110007767136

HINKEL kinesin, ANP MAPKKKs and MKK6/ANQ MAPKK, which phosphorylates and activates MPK4 MAPK, constitute a pathway that is required for cytokinesis in Arabidopsis thaliana

Takahashi Yuji,Soyano Takashi,Kosetsu Ken [他],SASABE Michiko,MACHIDA Yasunori
Plant and cell physiology 51(10), 1766-1776, 2010-10-01
NAID 10027353651

Related Pictures

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★リンクテーブル★

リンク元	「受容体チロシンキナーゼ」「MAPキナーゼ」「MAPキナーゼスーパーファミリーカスケード」「mitogen-activated protein kinase kinase」「MAPK kinase」
拡張検索	「MAPKKK」
関連記事	「MAP」

「受容体チロシンキナーゼ」

Search
PMC	articles
PubMed	articles
NCBI	proteins

Mitogen-activated protein kinase kinase
Identifiers
EC number	2.7.12.2
Databases
IntEnz	IntEnz view
BRENDA	BRENDA entry
ExPASy	NiceZyme view
KEGG	KEGG entry
MetaCyc	metabolic pathway
PRIAM	profile
PDB structures	RCSB PDB PDBe PDBsum
Search
PMC	articles
PubMed	articles
NCBI	proteins

　　[★]

英: receptor tyrosine kinase receptor, tyrosine kinase RTK
同？: チロシンキナーゼ受容体

カスケード

リガンド結合→レセプターの二量体化→レセプターの細胞膜内領域を自己リン酸化

→ホスホリパーゼC→ジアシルグリセロール→PKC→増殖因子の活性化

→Grb2→SOS→Ras→Raf-1(MAPKKK)→MEK(MAPKK)→Erk1/Erk2(MAPK)→(核移行)→ELK1→c-fos

→PI3キナーゼ→PI(3,4,5)P3→PDK1→PKB→増殖因子の活性化

「MAPキナーゼ」

　　[★]

英: MAP kinase, mitogen-activated protein kinase, MAPK
同: マイトジェン活性化プロテインキナーゼ、マップキナーゼ
関: MAPキナーゼスーパーファミリーカスケード。mitogen-activated protein

リン酸化部位：スレオニン、チロシン
MAPKKによってスレオニンとチロシン残基がリン酸化される。

MAPKスーパーファミリー

ERK1/ERK2
JNK1/JNK2/JNK3
p38α/p38β/p38γ/p38δ
ERK5

「MAPキナーゼスーパーファミリーカスケード」

　　[★]

層	増殖因子
細胞膜	Grb2 Sos Ras
細胞質
MAPKKKK	PAK3
MAPKKK	Raf-1/A-Raf
MAPKK	B-Raf/Mos
MAPK	MEK1/MEK2
基質	ERK1/ERK2, p90rsk, MNK1/MNK2, Sos, cPLA2, EGFR, Elk-1, Ets1, Sap1a, STAT, Map2, Tau

「mitogen-activated protein kinase kinase」

　　[★]

MAPキナーゼキナーゼ、マイトジェン活性化プロテインキナーゼキナーゼ

関: MAP kinase kinase、MAPK kinase、MAPK-ERK kinase、MAPKK、MEK

「MAPK kinase」

　　[★]

MAPキナーゼキナーゼ

関: MAP kinase kinase、MAPK-ERK kinase、MAPKK、MEK、mitogen-activated protein kinase kinase

「MAPKKK」

　　[★]

MAPキナーゼキナーゼキナーゼ

関: MAP kinase kinase kinase、MEK kinase、MEKK

「MAP」

　　[★]

僧帽弁輪形成術 mitral annuloplasty
Miller assessment for Pre-schoolers
平均動脈圧 mean arterial pressure
平均気道内圧 mean airway pressure
mannitol adenine phosphate
リン酸アンモニウムマグネシウム magnesium ammonium phosphate

[1] Dérijard B, et al. (1995). "Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms". Science. 267 (5198): 682–5. doi:10.1126/science.7839144. PMID 7839144.

[2] Dwivedi, Gaurav; Kemp, Melissa L. (February 15, 2012). "Systemic Redox Regulation of Cellular Information Processing". Antioxidants & Redox Signaling. 16: 374–80. doi:10.1089/ars.2011.4034. PMC 3279717. PMID 21939387.

[3] Falchook, Gerald S.; Lewis, Karl D.; Infante, Jeffrey R.; Gordon, Michael S.; Vogelzang, Nicholas J.; DeMarini, Douglas J.; Fecher, Leslie A.; et al. (2012). "Activity of the oral MEK inhibitor trametinib in patients with advanced melanoma: a phase 1 dose-escalation trial". The Lancet Oncology. 13 (8): 782–789. doi:10.1016/S1470-2045(12)70269-3. PMC 4109286. PMID 22805292.

v t e MAP kinase activation
Initiation	Mitogen
MAP kinase kinase kinase (MAP3K or MKKK)	MAP kinase kinase kinases MAP3K1 MAP3K2 MAP3K3 MAP3K4 MAP3K5 MAP3K6 MAP3K7 MAP3K8 RAFs RAF1 ARAF BRAF KSR1 KSR2) MLKs MAP3K12 MAP3K13 MAP3K9 MAP3K10 MAP3K11 MAP3K7 ZAK CDC7
MAP kinase kinase (MAP2K or MKK)	MAP2K1 MAP2K2 MAP2K3 MAP2K4 MAP2K5 MAP2K6 MAP2K7
MAP kinase	Extracellular signal-regulated kinases MAPK1 MAPK3 C-Jun N-terminal kinases MAPK8 MAPK9 MAPK10 P38 mitogen-activated protein kinases MAPK11 MAPK12 MAPK13 MAPK14 ERK5 kinase MAPK7 Atypical MAPKs MAPK4 MAPK6 MAPK15 NLK
Phosphatase	MAPK phosphatase

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

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案内

MAPKK