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PMID:18588859

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Citation

Browne, JA, Pearson, AL, Zahr, RA, Niculescu-Duvaz, I, Baines, DL and Dockrell, ME (2008) TGF-beta activates ERK5 in human renal epithelial cells. Biochem. Biophys. Res. Commun. 373:440-4

Abstract

The role of the MAP kinase, extracellular signal-regulated kinase 5 (ERK5) remains unknown, however it is involved in cell differentiation and survival as highlighted by the embryonic lethality of the ERK5 knockout. ERK5 can be activated by growth factors and other extracellular signals. TGF-beta, a powerful controller of epithelial cell phenotype, is known to activate the MAP kinase, ERK1/2 however its effect on ERK5 remains unknown. This study demonstrates, fort the first time, ERK5 activation by TGF-beta, observed in both transformed and primary adult human PTEC; activation required ALK-5 receptor activity. In addition this work demonstrates expression of myocyte enhancer factor-2 (MEF2C) by PTEC and that TGF-beta increased the association of MEK5 with phospho-ERK5 and MEF2C. ERK5 activation by either TGF-beta or epidermal growth factor (EGF) was also inhibited by the p38 MAP kinase inhibitor, SB-202190.

Links

PubMed Online version:10.1016/j.bbrc.2008.06.058

Keywords

Cell Line, Tumor; Epithelial Cells/drug effects; Epithelial Cells/enzymology; Humans; Imidazoles/pharmacology; Kidney/cytology; Kidney/drug effects; Kidney/enzymology; MADS Domain Proteins/metabolism; Mitogen-Activated Protein Kinase 7/metabolism; Myogenic Regulatory Factors/metabolism; Protein Kinase Inhibitors/pharmacology; Protein-Serine-Threonine Kinases; Pyridines/pharmacology; Receptors, Transforming Growth Factor beta/agonists; Transforming Growth Factor beta/antagonists & inhibitors; Transforming Growth Factor beta/pharmacology; p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors

Significance

Annotations

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

HUMAN:MEF2C

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13163

F

Seeded From UniProt

complete

HUMAN:MP2K5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q06413

F

Seeded From UniProt

complete

HUMAN:MP2K5

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13164

F

Seeded From UniProt

complete

HUMAN:MK07

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q13163

F

Seeded From UniProt

complete

HUMAN:MK07

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:MK07

involved_in

GO:0071560: cellular response to transforming growth factor beta stimulus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TGFB1

involved_in

GO:0006611: protein export from nucleus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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