Human tribbles, a protein family controlling mitogen-activated protein kinase cascades.
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.
Kiss-Toth
Endre
E
Cardiovascular Research Unit, University of Sheffield, Northern General Hospital, Sheffield S5 7AU, United Kingdom. E.Kiss-Toth@sheffield.ac.uk
Bagstaff
Stephanie M
SM
Sung
Hye Y
HY
Jozsa
Veronika
V
Dempsey
Clare
C
Caunt
Jim C
JC
Oxley
Kevin M
KM
Wyllie
David H
DH
Polgar
Timea
T
Harte
Mary
M
O'neill
Luke A J
LA
Qwarnstrom
Eva E
EE
Dower
Steven K
SK
D000818:Animals; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D029721:Drosophila Proteins / Q000737:chemistry / Q000502:physiology*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D047468:Immunoprecipitation; D007375:Interleukin-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000502:physiology*; D008156:Luciferases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000502:physiology* / Q000037:antagonists & inhibitors; D012097:Repressor Proteins; D014162:Transfection; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D007375:Interleukin-1; D016209:Interleukin-8; D047908:Intracellular Signaling Peptides and Proteins; D016376:Oligonucleotides, Antisense; D012097:Repressor Proteins; C493170:TRIB1 protein, human; C474831:TRIB3 protein, human; C410505:trbl protein, Drosophila; D008156:Luciferases; D017346:Protein Serine-Threonine Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C489044:TRIB2 protein, human; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases