Ser345
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Home > Phosphorylation Site Page: > Ser345  -  MLKL (mouse)

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

In vivo Characterization
Methods used to characterize site in vivo:
flow cytometry ( 21 ) , immunoassay ( 5 , 9 , 13 ) , immunoprecipitation ( 13 , 15 , 18 ) , mass spectrometry ( 13 ) , mass spectrometry (in vitro) ( 21 ) , mutation of modification site ( 11 , 18 , 19 , 21 ) , peptide sequencing ( 3 ) , phospho-antibody ( 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 20 ) , western blotting ( 3 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 )
Disease tissue studied:
atherosclerosis ( 20 ) , bone cancer ( 6 ) , colorectal cancer ( 5 , 11 , 17 , 18 , 19 ) , colorectal carcinoma ( 5 , 11 , 18 , 19 ) , lymphoma ( 11 , 19 ) , fibrosarcoma of soft tissue ( 3 , 7 , 11 , 18 )
Relevant cell line - cell type - tissue:
'brain, cerebral cortex' ( 9 ) , 3T3 (fibroblast) ( 11 , 18 ) , aorta ( 20 ) , CT26 (epithelial) ( 17 ) , fibroblast-embryo ( 18 ) , fibroblast-skin ( 11 , 19 , 21 ) , HEK293T (epithelial) ( 5 ) , HeLa (cervical) ( 18 ) , HT-29 (intestinal) ( 5 , 11 , 18 , 19 ) , L929 (fibroblast) ( 3 , 7 , 11 , 18 ) , macrophage-bone marrow ( 6 , 8 , 12 , 13 , 14 ) , MEF (fibroblast) ( 3 , 5 , 7 , 13 , 15 , 16 ) , microvessel endothelial-lung ( 10 ) , neuron-brain ( 9 ) , SVEC (endothelial) ( 18 ) , testis ( 5 ) , U-937 (myeloid) ( 11 , 19 )

Upstream Regulation
Regulatory protein:
CK1G2 (mouse) ( 5 ) , FADD (mouse) ( 17 ) , FAM105B (human) ( 13 ) , IFNB1 (mouse) ( 14 ) , MAPKAPK2 (mouse) ( 8 ) , MYD88 (mouse) ( 8 ) , RIPK1 (mouse) ( 9 ) , RIPK3 (human) ( 3 ) , RIPK3 (mouse) ( 5 , 9 , 17 ) , SPATA2 (mouse) ( 16 ) , STING (mouse) ( 14 ) , TICAM1 (mouse) ( 8 ) , TTP (mouse) ( 8 ) , ULK1 (human) ( 7 )
Putative in vivo kinases:
RIPK3 (human) ( 5 , 18 )
Kinases, in vitro:
RIPK3 (mouse) ( 21 )
Treatments:
development ( 5 ) , GSK'872 ( 3 , 18 ) , GW440139B ( 18 ) , ischemia/reperfusion ( 9 ) , LPS ( 5 , 6 , 8 , 14 ) , LY2228820 ( 8 ) , Necrostatin-1 ( 10 ) , phenhydan ( 11 ) , Q-VD-OPh ( 3 ) , SM-164 ( 15 ) , TNF ( 3 , 5 , 7 , 8 , 10 , 11 , 13 , 15 , 18 ) , TRAIL ( 5 ) , Z-IETD-fmk ( 8 ) , Z-VAD-FMK ( 5 , 6 , 7 , 8 , 11 , 12 , 13 , 14 , 15 , 18 )

Downstream Regulation
Effects of modification on MLKL:
activity, induced ( 18 ) , intracellular localization ( 18 ) , protein conformation ( 18 )
Effects of modification on biological processes:
apoptosis, induced ( 6 , 10 , 11 ) , signaling pathway regulation ( 8 )

References 

1

Gao XQ, et al. (2021) The circRNA CNEACR regulates necroptosis of cardiomyocytes through Foxa2 suppression. Cell Death Differ
34588633   Curated Info

2

Patankar JV, et al. (2021) E-type prostanoid receptor 4 drives resolution of intestinal inflammation by blocking epithelial necroptosis. Nat Cell Biol 23, 796-807
34239062   Curated Info

3

Wu W, et al. (2021) TNF-induced necroptosis initiates early autophagy events via RIPK3-dependent AMPK activation, but inhibits late autophagy. Autophagy, 1-18
33779513   Curated Info

4

Wu P, Cai M, Liu J, Wang X (2021) Catecholamine Surges Cause Cardiomyocyte Necroptosis a RIPK1-RIPK3-Dependent Pathway in Mice. Front Cardiovasc Med 8, 740839
34604361   Curated Info

5

Li D, et al. (2020) Casein kinase 1G2 suppresses necroptosis-promoted testis aging by inhibiting receptor-interacting kinase 3. Elife 9
33206046   Curated Info

6

Hao Q, et al. (2020) Enhanced RIPK3 kinase activity-dependent lytic cell death in M1 but not M2 macrophages. Mol Immunol
33221042   Curated Info

7

Wu W, et al. (2020) The Autophagy-Initiating Kinase ULK1 Controls RIPK1-Mediated Cell Death. Cell Rep 31, 107547
32320653   Curated Info

8

Ariana A, et al. (2020) Tristetraprolin regulates necroptosis during tonic Toll-like receptor 4 (TLR4) signaling in murine macrophages. J Biol Chem
32094226   Curated Info

9

Naito MG, et al. (2020) Sequential activation of necroptosis and apoptosis cooperates to mediate vascular and neural pathology in stroke. Proc Natl Acad Sci U S A
32071228   Curated Info

10

Fritsch M, et al. (2019) Caspase-8 is the molecular switch for apoptosis, necroptosis and pyroptosis. Nature 575, 683-687
31748744   Curated Info

11

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

12

Sarhan J, et al. (2018) Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during infection. Proc Natl Acad Sci U S A 115, E10888-E10897
30381458   Curated Info

13

Heger K, et al. (2018) OTULIN limits cell death and inflammation by deubiquitinating LUBAC. Nature 559, 120-124
29950720   Curated Info

14

Sarhan J, et al. (2018) Constitutive interferon signaling maintains critical threshold of MLKL expression to license necroptosis. Cell Death Differ
29786074   Curated Info

15

Wang H, et al. (2017) PELI1 functions as a dual modulator of necroptosis and apoptosis by regulating ubiquitination of RIPK1 and mRNA levels of c-FLIP. Proc Natl Acad Sci U S A 114, 11944-11949
29078411   Curated Info

16

Wei R, et al. (2017) SPATA2 regulates the activation of RIPK1 by modulating linear ubiquitination. Genes Dev 31, 1162-1176
28701375   Curated Info

17

Aaes TL, et al. (2016) Vaccination with Necroptotic Cancer Cells Induces Efficient Anti-tumor Immunity. Cell Rep 15, 274-87
27050509   Curated Info

18

Rodriguez DA, et al. (2016) Characterization of RIPK3-mediated phosphorylation of the activation loop of MLKL during necroptosis. Cell Death Differ 23, 76-88
26024392   Curated Info

19

Tanzer MC, et al. (2015) Necroptosis signalling is tuned by phosphorylation of MLKL residues outside the pseudokinase domain activation loop. Biochem J 471, 255-65
26283547   Curated Info

20

Meng L, Jin W, Wang X (2015) RIP3-mediated necrotic cell death accelerates systematic inflammation and mortality. Proc Natl Acad Sci U S A 112, 11007-12
26283397   Curated Info

21

Murphy JM, et al. (2013) The pseudokinase MLKL mediates necroptosis via a molecular switch mechanism. Immunity 39, 443-53
24012422   Curated Info