Ser358
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Home > Phosphorylation Site Page: > Ser358  -  MLKL (human)

Site Information
ELRkTQtsMSLGTtR   SwissProt Entrez-Gene
Blast this site against: NCBI  SwissProt  PDB 
Site Group ID: 22996309

In vivo Characterization
Methods used to characterize site in vivo:
[32P] ATP in vitro ( 11 ) , immunoassay ( 3 , 5 , 7 , 10 ) , immunoprecipitation ( 9 , 11 ) , mass spectrometry ( 11 ) , mutation of modification site ( 10 , 11 ) , phospho-antibody ( 1 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 ) , western blotting ( 1 , 3 , 4 , 5 , 6 , 7 , 9 , 10 )
Disease tissue studied:
Alzheimer's disease ( 8 ) , breast cancer ( 5 ) , breast adenocarcinoma ( 5 ) , breast cancer, triple negative ( 5 ) , colorectal cancer ( 4 , 6 , 7 , 9 , 10 , 11 ) , colorectal carcinoma ( 4 , 6 , 7 , 9 , 10 , 11 ) , leukemia ( 4 ) , T cell leukemia ( 4 ) , lymphoma ( 6 , 10 ) , fibrosarcoma of soft tissue ( 6 )
Relevant cell line - cell type - tissue:
3T3 (fibroblast) ( 6 ) , brain ( 8 ) , BT-474 (breast cell) ( 5 ) , HCC1806 (breast cell) ( 5 ) , HCT116 (intestinal) ( 7 ) , HeLa (cervical) ( 3 , 10 , 11 ) , HT-29 (intestinal) ( 4 , 6 , 9 , 10 , 11 ) , Jurkat (T lymphocyte) ( 4 ) , L929 (fibroblast) ( 6 ) , liver ( 10 ) , MDA-MB-361 (breast cell) ( 5 ) , MDA-MB-453 (breast cell) ( 5 ) , MDA-MB-468 (breast cell) ( 5 ) , platelet ( 1 ) , SW480 (intestinal) ( 7 ) , U-937 (myeloid) ( 6 , 10 )

Upstream Regulation
Regulatory protein:
RIPK3 (human) ( 3 ) , TIF1B (human) ( 4 )
Putative in vivo kinases:
RIPK3 (human) ( 7 , 10 , 11 )
Kinases, in vitro:
RIPK3 (human) ( 2 , 11 )
Treatments:
adriamycin ( 5 ) , Akt_inhibitor_VIII ( 1 ) , BV6 ( 5 ) , GSK'843 ( 1 ) , GSK'872 ( 1 ) , LPS ( 10 ) , LY294002 ( 1 ) , Necrostatin-1 ( 3 , 10 ) , phenhydan ( 6 ) , resibufogenin ( 7 ) , siRNA ( 7 ) , smac ( 3 ) , thrombin ( 1 ) , TNF ( 3 , 4 , 5 , 6 , 10 ) , virus infection ( 5 ) , wortmannin ( 1 ) , Z-VAD-FMK ( 3 , 5 , 6 , 10 )

Downstream Regulation
Effects of modification on MLKL:
intracellular localization ( 5 , 8 , 9 , 10 ) , molecular association, regulation ( 10 ) , protein conformation ( 8 , 9 )
Effects of modification on biological processes:
apoptosis, induced ( 5 , 10 ) , carcinogenesis, inhibited ( 7 ) , cell motility, inhibited ( 7 ) , signaling pathway regulation ( 11 ) , transcription, induced ( 7 )
Induce interaction with:
MLKL (human) ( 10 )

Disease / Diagnostics Relevance
Relevant diseases:
Alzheimer's disease ( 8 ) , colorectal cancer ( 7 )

References 

1

Ekhlak M, et al. (2023) Necroptosis executioner MLKL plays pivotal roles in agonist-induced platelet prothrombotic responses and lytic cell death in a temporal order. Cell Death Differ
37301927   Curated Info

2

Lee SA, et al. (2023) OASL phase condensation induces amyloid-like fibrillation of RIPK3 to promote virus-induced necroptosis. Nat Cell Biol 25, 92-107
36604592   Curated Info

3

Chen X, et al. (2022) Mosaic composition of RIP1-RIP3 signalling hub and its role in regulating cell death. Nat Cell Biol
35256774   Curated Info

4

Zu R, et al. (2021) Quantitative analysis of phosphoproteome in necroptosis reveals a role of TRIM28 phosphorylation in promoting necroptosis-induced cytokine production. Cell Death Dis 12, 994
34689152   Curated Info

5

Zhang J, et al. (2021) Necroptotic virotherapy of oncolytic alphavirus M1 cooperated with Doxorubicin displays promising therapeutic efficacy in TNBC. Oncogene 40
34155344   Curated Info

6

Moerke C, et al. (2018) The anticonvulsive Phenhydan suppresses extrinsic cell death. Cell Death Differ
30442947   Curated Info

7

Han Q, et al. (2018) Resibufogenin suppresses colorectal cancer growth and metastasis through RIP3-mediated necroptosis. J Transl Med 16, 201
30029665   Curated Info

8

Caccamo A, et al. (2017) Necroptosis activation in Alzheimer's disease. Nat Neurosci 20, 1236-1246
28758999   Curated Info

9

Yoon S, Bogdanov K, Kovalenko A, Wallach D (2016) Necroptosis is preceded by nuclear translocation of the signaling proteins that induce it. Cell Death Differ 23, 253-60
26184911   Curated Info

10

Wang H, et al. (2014) Mixed Lineage Kinase Domain-like Protein MLKL Causes Necrotic Membrane Disruption upon Phosphorylation by RIP3. Mol Cell 54, 133-46
24703947   Curated Info

11

Sun L, et al. (2012) Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase. Cell 148, 213-27
22265413   Curated Info

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