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PMID:15299019

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Citation

Kiss-Toth, E, Bagstaff, SM, Sung, HY, Jozsa, V, Dempsey, C, Caunt, JC, Oxley, KM, Wyllie, DH, Polgar, T, Harte, M, O'neill, LA, Qwarnstrom, EE and Dower, SK (2004) Human tribbles, a protein family controlling mitogen-activated protein kinase cascades. J. Biol. Chem. 279:42703-8

Abstract

Control of mitogen-activated protein kinase (MAPK) cascades is central to regulation of many cellular responses. We describe here human tribbles homologues (Htrbs) that control MAPK activity. MAPK kinases interact with Trbs and regulate their steady state levels. Further, Trbs selectively regulate the activation of extracellular signal-regulated kinases, c-Jun NH2-terminal kinases, and p38 MAPK with different relative levels of activity for the three classes of MAPK observed depending on the level of Trb expression. These results suggest that Trbs control both the extent and the specificity of MAPK kinase activation of MAPK.

Links

PubMed Online version:10.1074/jbc.M407732200

Keywords

Animals; Blotting, Western; Cell Cycle Proteins/chemistry; Cell Cycle Proteins/physiology; Dose-Response Relationship, Drug; Drosophila Proteins/chemistry; Drosophila Proteins/physiology; Enzyme Activation; Gene Expression Regulation; Genes, Reporter; HeLa Cells; Humans; Immunoprecipitation; Interleukin-1/metabolism; Interleukin-8/metabolism; Intracellular Signaling Peptides and Proteins/chemistry; Intracellular Signaling Peptides and Proteins/physiology; Luciferases/metabolism; MAP Kinase Signaling System; Mice; Mitogen-Activated Protein Kinases/metabolism; Models, Biological; Molecular Sequence Data; NIH 3T3 Cells; Oligonucleotides, Antisense/chemistry; Plasmids/metabolism; Protein Binding; Protein-Serine-Threonine Kinases/chemistry; Protein-Serine-Threonine Kinases/physiology; Repressor Proteins; Transfection; p38 Mitogen-Activated Protein Kinases/metabolism

Significance

Annotations

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

HUMAN:MP2K7

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96RU7

F

Seeded From UniProt

complete

HUMAN:MP2K1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q96RU7

F

Seeded From UniProt

complete

HUMAN:TRIB1

involved_in

GO:0006469: negative regulation of protein kinase activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TRIB1

enables

GO:0031434: mitogen-activated protein kinase kinase binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:TRIB1

enables

GO:0004860: protein kinase inhibitor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:TRIB1

involved_in

GO:0043433: negative regulation of DNA-binding transcription factor activity

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TRIB1

involved_in

GO:0043405: regulation of MAP kinase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TRIB3

involved_in

GO:0043405: regulation of MAP kinase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TRIB3

enables

GO:0019901: protein kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:O14733

F

Seeded From UniProt

complete

HUMAN:TRIB3

enables

GO:0019901: protein kinase binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q02750

F

Seeded From UniProt

complete


See also

References

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