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PMID:22291017

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Citation

Fidalgo, M, Guerrero, A, Fraile, M, Iglesias, C, Pombo, CM and Zalvide, J (2012) Adaptor protein cerebral cavernous malformation 3 (CCM3) mediates phosphorylation of the cytoskeletal proteins ezrin/radixin/moesin by mammalian Ste20-4 to protect cells from oxidative stress. J. Biol. Chem. 287:11556-65

Abstract

While studying the functions of CCM3/PDCD10, a gene encoding an adaptor protein whose mutation results in vascular malformations, we have found that it is involved in a novel response to oxidative stress that results in phosphorylation and activation of the ezrin/radixin/moesin (ERM) family of proteins. This phosphorylation protects cells from accidental cell death induced by oxidative stress. We also present evidence that ERM phosphorylation is performed by the GCKIII kinase Mst4, which is activated and relocated to the cell periphery after oxidative stress. The cellular levels of Mst4 and its activation after oxidative stress depend on the presence of CCM3, as absence of the latter impairs the phosphorylation of ERM proteins and enhances death of cells exposed to reactive oxygen species. These findings shed new light on the response of cells to oxidative stress and identify an important pathophysiological situation in which ERM proteins and their phosphorylation play a significant role.

Links

PubMed PMC3322875 Online version:10.1074/jbc.M111.320259

Keywords

Animals; Apoptosis Regulatory Proteins/metabolism; Cell Death; Cell Line; Cytoskeletal Proteins/metabolism; Humans; Membrane Proteins/metabolism; Microfilament Proteins/metabolism; Oxidative Stress; Phosphoproteins/metabolism; Phosphorylation; Protein Transport; Protein-Serine-Threonine Kinases/metabolism; Proto-Oncogene Proteins/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:STK25

involved_in

GO:0042542: response to hydrogen peroxide

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:EZRI

located_in

GO:0071944: cell periphery

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MOES

located_in

GO:0071944: cell periphery

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:RADI

located_in

GO:0071944: cell periphery

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:PDC10

involved_in

GO:0042542: response to hydrogen peroxide

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:STK26

located_in

GO:0048471: perinuclear region of cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:STK26

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:STK26

involved_in

GO:0006468: protein phosphorylation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • has_input:(UniProtKB:P35241)|has_input:(UniProtKB:P26038)|has_input:(UniProtKB:P15311)

Seeded From UniProt

complete

HUMAN:STK26

located_in

GO:0071944: cell periphery

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:STK26

located_in

GO:0005794: Golgi apparatus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:STK26

involved_in

GO:0042542: response to hydrogen peroxide

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:STK26

involved_in

GO:1903205: regulation of hydrogen peroxide-induced cell death

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:STK24

involved_in

GO:0042542: response to hydrogen peroxide

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:F5H1A7

part_of

GO:0071944: cell periphery

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:EZRI

part_of

GO:0071944: cell periphery

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

Notes

See also

References

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