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Mitogen-aktivirana protein
kinaza kinaza kinaza 1
Mitogen-aktivirana protein; kinaza kinaza kinaza 1
Identifikatori
Simboli	MAP3K1; MAPKKK1; MEKK; MEKK1
Vanjski ID	OMIM: 600982 MGI: 1346872 HomoloGene: 8056 GeneCards: MAP3K1 Gene
Ontologija gena
Molekularna funkcija	• nukleotidno vezivanje; • vezivanje magnezijum jona; • aktivnost protein serin/treonin kinaze; • aktivnost MAP kinaza kinaza kinaze; • proteinsko vezivanje; • ATP vezivanje; • vezivanje jona cinka; • aktivnost transferaze;
Celularna komponenta	• celularna komponenta;
Biološki proces	• proteinska aminokiselinska fosforilacija; • signalni put receptora transformacionog faktora rasta beta; • apoptotičke mitohondrijalne promene; • regulacija ćelijske migracije; • pozitivna regulacija aktin filamentne polimerizacije; • lečenje rana;
Pregled RNK izražavanja
	podaci
Ortolozi
Vrsta	Čovek
Entrez	4214
Ensembl	ENSG00000095015
UniProt	Q13233
RefSeq (mRNA)	XM_001128827
RefSeq (protein)	XP_001128827
Lokacija (UCSC)	Chr 5:; 56.15 - 56.23 Mb
PubMed pretraga	[1]

Mitogen-aktivirana protein kinaza kinaza kinaza 1 je enzim koji je kod ljudi kodiran MAP3K1 genom.^[1]^[2]

MAP3K, ili MEK kinaza, je serin/treonin kinaza koja ima ključnu ulogu u mreži enzima fosforilacije koji integrišu ćelijske odgovore na brojne mitogene i metaboličke stimuluse, uključujući insulin (MIM 176730) i mnoge faktore rasta.^[2]

Genetika miša je ustanovila da je ova kinaza važna u: korektnoj embriogenezi, keratinocit migraciji, T ćelijskoj citokinskoj produkciji i B ćelijskoj produkciji antitela.

Interakcije

Za MAP3K1 je bilo pokazano da interaguje sa C-Raf,^[3] MAPK8,^[4] TRAF2,^[5] MAP2K1,^[3] Grb2,^[6] MAPK1,^[3] AXIN1^[7]^[8] i UBE2I.^[9]

Reference

^ Vinik BS, Kay ES, Fiedorek FT Jr (1996). „Mapping of the MEK kinase gene (Mekk) to mouse chromosome 13 and human chromosome 5”. Mamm Genome. 6 (11): 782—3. PMID 8597633.
^ ^а ^б „Entrez Gene: MAP3K1 mitogen-activated protein kinase kinase kinase 1”.
^ ^а ^б ^в Karandikar, M; Xu S; Cobb M H (2000). „MEKK1 binds raf-1 and the ERK2 cascade components”. J. Biol. Chem. UNITED STATES. 275 (51): 40120—7. ISSN 0021-9258. PMID 10969079. doi:10.1074/jbc.M005926200.
^ Xu, S; Cobb M H (1997). „MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases”. J. Biol. Chem. UNITED STATES. 272 (51): 32056—60. ISSN 0021-9258. PMID 9405400.
^ Baud, V; Liu Z G; et al. (1999). „Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain”. Genes Dev. UNITED STATES. 13 (10): 1297—308. ISSN 0890-9369. PMC 316725 . PMID 10346818.
^ Pomérance, M; Multon M C; et al. (1998). „Grb2 interaction with MEK-kinase 1 is involved in regulation of Jun-kinase activities in response to epidermal growth factor”. J. Biol. Chem. UNITED STATES. 273 (38): 24301—4. ISSN 0021-9258. PMID 9733714.
^ Zhang, Yi; Qiu Wen-Jie; et al. (2002). „Casein kinase I and casein kinase II differentially regulate axin function in Wnt and JNK pathways”. J. Biol. Chem. United States. 277 (20): 17706—12. ISSN 0021-9258. PMID 11884395. doi:10.1074/jbc.M111982200.
^ Zhang, Y; Neo S Y; et al. (2000). „Dimerization choices control the ability of axin and dishevelled to activate c-Jun N-terminal kinase/stress-activated protein kinase”. J. Biol. Chem. UNITED STATES. 275 (32): 25008—14. ISSN 0021-9258. PMID 10829020. doi:10.1074/jbc.M002491200.
^ Saltzman, A; Searfoss G; et al. (1998). „hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity”. FEBS Lett. NETHERLANDS. 425 (3): 431—5. ISSN 0014-5793. PMID 9563508.

Literatura

Lee FS, Hagler J, Chen ZJ, Maniatis T (1997). „Activation of the IkappaB alpha kinase complex by MEKK1, a kinase of the JNK pathway.”. Cell. 88 (2): 213—22. PMID 9008162. doi:10.1016/S0092-8674(00)81842-5.
Siow YL; Kalmar GB; Sanghera JS; et al. (1997). „Identification of two essential phosphorylated threonine residues in the catalytic domain of Mekk1. Indirect activation by Pak3 and protein kinase C.”. J. Biol. Chem. 272 (12): 7586—94. PMID 9065412. doi:10.1074/jbc.272.12.7586.
Su YC; Han J; Xu S; et al. (1997). „NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain.”. EMBO J. 16 (6): 1279—90. PMC 1169726 . PMID 9135144. doi:10.1093/emboj/16.6.1279.
Wu Z, Wu J, Jacinto E, Karin M (1997). „Molecular cloning and characterization of human JNKK2, a novel Jun NH2-terminal kinase-specific kinase.”. Mol. Cell. Biol. 17 (12): 7407—16. PMC 232596 . PMID 9372971.
Xu S, Cobb MH (1998). „MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases.”. J. Biol. Chem. 272 (51): 32056—60. PMID 9405400. doi:10.1074/jbc.272.51.32056.
Fanger GR; Widmann C; Porter AC; et al. (1998). „14-3-3 proteins interact with specific MEK kinases.”. J. Biol. Chem. 273 (6): 3476—83. PMID 9452471. doi:10.1074/jbc.273.6.3476.
Hirai S; Noda K; Moriguchi T; et al. (1998). „Differential activation of two JNK activators, MKK7 and SEK1, by MKN28-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2.”. J. Biol. Chem. 273 (13): 7406—12. PMID 9516438. doi:10.1074/jbc.273.13.7406.
Saltzman A; Searfoss G; Marcireau C; et al. (1998). „hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity.”. FEBS Lett. 425 (3): 431—5. PMID 9563508. doi:10.1016/S0014-5793(98)00287-7.
Guan Z; Buckman SY; Pentland AP; et al. (1998). „Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway.”. J. Biol. Chem. 273 (21): 12901—8. PMID 9582321. doi:10.1074/jbc.273.21.12901.
Lee FS, Peters RT, Dang LC, Maniatis T (1998). „MEKK1 activates both IkappaB kinase alpha and IkappaB kinase beta.”. Proc. Natl. Acad. Sci. U.S.A. 95 (16): 9319—24. PMC 21336 . PMID 9689078. doi:10.1073/pnas.95.16.9319.
Yuasa T, Ohno S, Kehrl JH, Kyriakis JM (1998). „Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38.”. J. Biol. Chem. 273 (35): 22681—92. PMID 9712898.
Pomérance M; Multon MC; Parker F; et al. (1998). „Grb2 interaction with MEK-kinase 1 is involved in regulation of Jun-kinase activities in response to epidermal growth factor.”. J. Biol. Chem. 273 (38): 24301—4. PMID 9733714. doi:10.1074/jbc.273.38.24301.
Xia Y; Wu Z; Su B; et al. (1998). „JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extension.”. Genes Dev. 12 (21): 3369—81. PMC 317229 . PMID 9808624. doi:10.1101/gad.12.21.3369.
Nemoto S, DiDonato JA, Lin A (1998). „Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase.”. Mol. Cell. Biol. 18 (12): 7336—43. PMC 109315 . PMID 9819420.
Yujiri T, Sather S, Fanger GR, Johnson GL (1998). „Role of MEKK1 in cell survival and activation of JNK and ERK pathways defined by targeted gene disruption.”. Science. 282 (5395): 1911—4. PMID 9836645. doi:10.1126/science.282.5395.1911.
Baud V; Liu ZG; Bennett B; et al. (1999). „Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain.”. Genes Dev. 13 (10): 1297—308. PMC 316725 . PMID 10346818. doi:10.1101/gad.13.10.1297.
Kopp E; Medzhitov R; Carothers J; et al. (1999). „ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway.”. Genes Dev. 13 (16): 2059—71. PMC 316957 . PMID 10465784. doi:10.1101/gad.13.16.2059.
Ito M; Yoshioka K; Akechi M; et al. (1999). „JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway.”. Mol. Cell. Biol. 19 (11): 7539—48. PMC 84763 . PMID 10523642.
Minamino T; Yujiri T; Papst PJ; et al. (2000). „MEKK1 suppresses oxidative stress-induced apoptosis of embryonic stem cell-derived cardiac myocytes.”. Proc. Natl. Acad. Sci. U.S.A. 96 (26): 15127—32. PMC 24784 . PMID 10611349. doi:10.1073/pnas.96.26.15127.
Nicholas C. Price; Lewis Stevens (1999). Fundamentals of Enzymology: The Cell and Molecular Biology of Catalytic Proteins (Third изд.). USA: Oxford University Press. ISBN 019850229X.
Eric J. Toone (2006). Advances in Enzymology and Related Areas of Molecular Biology, Protein Evolution (Volume 75 изд.). Wiley-Interscience. ISBN 0471205036.
Branden C; Tooze J. Introduction to Protein Structure. New York, NY: Garland Publishing. ISBN 0-8153-2305-0.
Irwin H. Segel. Enzyme Kinetics: Behavior and Analysis of Rapid Equilibrium and Steady-State Enzyme Systems (Book 44 изд.). Wiley Classics Library. ISBN 0471303097.
William P. Jencks (1987). Catalysis in Chemistry and Enzymology. Dover Publications. ISBN 0486654605.

Spoljašnje veze

[pmid8597633-1] Vinik BS, Kay ES, Fiedorek FT Jr (1996). „Mapping of the MEK kinase gene (Mekk) to mouse chromosome 13 and human chromosome 5”. Mamm Genome. 6 (11): 782—3. PMID 8597633.

[entrez-2] а ^б „Entrez Gene: MAP3K1 mitogen-activated protein kinase kinase kinase 1”.

[pmid10969079-3] а ^б ^в Karandikar, M; Xu S; Cobb M H (2000). „MEKK1 binds raf-1 and the ERK2 cascade components”. J. Biol. Chem. UNITED STATES. 275 (51): 40120—7. ISSN 0021-9258. PMID 10969079. doi:10.1074/jbc.M005926200.

[pmid9405400-4] Xu, S; Cobb M H (1997). „MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases”. J. Biol. Chem. UNITED STATES. 272 (51): 32056—60. ISSN 0021-9258. PMID 9405400.

[pmid10346818-5] Baud, V; Liu Z G; et al. (1999). „Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain”. Genes Dev. UNITED STATES. 13 (10): 1297—308. ISSN 0890-9369. PMC 316725 . PMID 10346818.

[pmid9733714-6] Pomérance, M; Multon M C; et al. (1998). „Grb2 interaction with MEK-kinase 1 is involved in regulation of Jun-kinase activities in response to epidermal growth factor”. J. Biol. Chem. UNITED STATES. 273 (38): 24301—4. ISSN 0021-9258. PMID 9733714.

[pmid11884395-7] Zhang, Yi; Qiu Wen-Jie; et al. (2002). „Casein kinase I and casein kinase II differentially regulate axin function in Wnt and JNK pathways”. J. Biol. Chem. United States. 277 (20): 17706—12. ISSN 0021-9258. PMID 11884395. doi:10.1074/jbc.M111982200.

[pmid10829020-8] Zhang, Y; Neo S Y; et al. (2000). „Dimerization choices control the ability of axin and dishevelled to activate c-Jun N-terminal kinase/stress-activated protein kinase”. J. Biol. Chem. UNITED STATES. 275 (32): 25008—14. ISSN 0021-9258. PMID 10829020. doi:10.1074/jbc.M002491200.

[pmid9563508-9] Saltzman, A; Searfoss G; et al. (1998). „hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity”. FEBS Lett. NETHERLANDS. 425 (3): 431—5. ISSN 0014-5793. PMID 9563508.

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