Mitogen-activated protein kinase kinase kinase

From Proteopedia

Function Mitogen-activated protein kinase kinase kinase or DLK (MAP3K) are serine/threonine kinases which regulate various cellular activities in response to extracellular stimuli by mitogens, heat shock and more. MAP3K is part of the MAPK cascade which consists also of MAPK and MAP2K which are activated by phosphorylation. MAP3K activates MAP2K[1]. MAP3K1 regulates cell migration and contributes to pro-survival signaling[2]. MAP3K10 has a role in the tumorugenesis of pancreatic ductal adenocarcinoma[3]. MAP3K14 is a regulator of enforced viral replication in the spleen[4]. Disease MAP3K1 mutations are observed in various cancer types and in particular in luminal beast cancer[5].

spinqualitylabelsall models Mitogen-activated protein kinase kinase kinase 3 (green) complex with MAP2K5 PHOX domain (grey) (PDB code 2o2v). Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

3D Structures of Mitogen-activated protein kinase kinase kinase

Updated on 11-July-2024

MAP3K1; Domains – kinase 10-307; SH3-binding 465-480; TOG 648-867

6nfy, 6nfz - hMAP3K1 kinase domain + cancer drug - human

6ng0 - hMAP3K1 kinase domain (mutant) + cancer drug

6nyb - hMAP3K1 kinase domain (mutant) + B-raf + 14-3-3 protein ζ – Cryo EM

6whb - hMAP3K1 TOG domain + cancer drug

1uti - MAP3K1 SH3-binding domain +GRB2-related adaptor protein 2 - mouse

MAP3K2

2cu1 - hMAP3K2 PB1 domain (mutant) - NMR

2o2v, 5uoj – hMAP3K2+hMAP3K

2npt - hMAP3K2 PHOX domain + hMAP2K5 PHOX domain

MAP3K3

2c60 – hMAP3K3 PHOX domain

2jrh - hMAP3K3 PB1 domain

2pph - hMAP3K3 PB1 domain - NMR

MAP3K5 (Ask1; Apoptosis signal-regulating kinase 1)

2clq – hMAP3K5

6oyt, 6vre, 6xih, 7mu7 - hMAP3K5 + inhibitor

4bf2, 4bhn, 4bib, 4bic, 4bid, 4bie, 6e2m, 6e2n, 6e2o, 6oyw - hMAP3K5 (mutant) + inhibitor

MAP3K7 (TAK1)

2eva – hMAP3K7/MAP3K7-interacting protein 1

2y1y, 4gs4, 4l3p, 4l52, 4l53, 4o91, 5gjd, 5gjf, 5gjg, 5e7r, 5jga, 5jgb, 5jgd, 7nth - hMAP3K7/MAP3K7-interacting protein 1 + inhibitor

MAP3K9

3dtc - hMAP3K9 (mutant) + inhibitor

MAP3K10

2rf0 - hMAP3K10 SH3 domain - NMR

MAP3K11

6cq7 - hMAP3K11 SH3 domain/huntington fusion peptide

MAP3K12 kinase domain 115-402

5cen - hMAP3K12

5ceo, 8deg - hMAP3K12 + inhibitor

MAP3K14 kinase domain 343-686 (NIK)

4dn5 - hMAP3K14 (mutant) + ATP-γ-S

4idt, 4idv, 6wpp, 6z1q, 6z1t - hMAP3K14 + inhibitor

6g4y, 6g4z, 6myn, 7szr - mMAP3K14 + inhibitor

MAP3K15

6v0m - hMAP3K15 residues 1241-1308

MAP3K MLT

6jut, 6juu - hMAP3K + inhibitor

References

1. ↑ Ellinger-Ziegelbauer H, Brown K, Kelly K, Siebenlist U. Direct activation of the stress-activated protein kinase (SAPK) and extracellular signal-regulated protein kinase (ERK) pathways by an inducible mitogen-activated protein Kinase/ERK kinase kinase 3 (MEKK) derivative. J Biol Chem. 1997 Jan 31;272(5):2668-74. PMID:9006902
2. ↑ Pham TT, Angus SP, Johnson GL. MAP3K1: Genomic Alterations in Cancer and Function in Promoting Cell Survival or Apoptosis. Genes Cancer. 2013 Nov;4(11-12):419-26. PMID:24386504 doi:10.1177/1947601913513950
3. ↑ An Y, Cai B, Chen J, Lv N, Yao J, Xue X, Tu M, Tang D, Wei J, Jiang K, Wu J, Li Q, Gao W, Miao Y. MAP3K10 promotes the proliferation and decreases the sensitivity of pancreatic cancer cells to gemcitabine by upregulating Gli-1 and Gli-2. Cancer Lett. 2013 Feb 28;329(2):228-35. PMID:23178452 doi:10.1016/j.canlet.2012.11.005
4. ↑ Hamdan TA, Bhat H, Cham LB, Adomati T, Lang J, Li F, Murtaza A, Hardt C, Lang PA, Duhan V, Lang KS. Map3k14 as a Regulator of Innate and Adaptive Immune Response during Acute Viral Infection. Pathogens. 2020 Feb 4;9(2):96. PMID:32033109 doi:10.3390/pathogens9020096
5. ↑ Santen RJ, Song RX, McPherson R, Kumar R, Adam L, Jeng MH, Yue W. The role of mitogen-activated protein (MAP) kinase in breast cancer. J Steroid Biochem Mol Biol. 2002 Feb;80(2):239-56. PMID:11897507