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TGF-beta activates ERK5 in human renal epithelial cells
James Alexander Browne1, Alexander L Pearson, Riad Abou Zahr
1South West Thames Institute for Renal Research, St. Helier Hospital, Carshalton, Surrey SM5 1AA, UK. james.browne@epsom-sthelier.nhs.uk
Biochemical and Biophysical Research Communications
|July 1, 2008
Summary
Extracellular signal-regulated kinase 5 (ERK5) is activated by transforming growth factor-beta (TGF-beta) in human kidney cells. This pathway involves the ALK-5 receptor and MEF2C, impacting cell phenotype and survival.
Area of Science:
- Cellular Biology
- Molecular Signaling
- Signal Transduction
Background:
- Extracellular signal-regulated kinase 5 (ERK5) plays a role in cell differentiation and survival, evidenced by embryonic lethality in ERK5 knockout models.
- Transforming growth factor-beta (TGF-beta) is a key regulator of epithelial cell phenotype, known to activate ERK1/2 but its effect on ERK5 is uncharacterized.
Purpose of the Study:
- To investigate the effect of TGF-beta on ERK5 activation in human proximal tubule epithelial cells (PTEC).
- To elucidate the downstream signaling components and receptors involved in TGF-beta-mediated ERK5 activation.
Main Methods:
- Utilized transformed and primary adult human PTEC.
- Assessed ERK5 activation through biochemical assays.
- Investigated the role of ALK-5 receptor activity and myocyte enhancer factor-2 (MEF2C) association with ERK5.
- Examined the effect of p38 MAP kinase inhibitor (SB-202190) on ERK5 activation.
Main Results:
- Demonstrated, for the first time, TGF-beta-induced activation of ERK5 in both transformed and primary human PTEC.
- Confirmed that TGF-beta-mediated ERK5 activation is dependent on ALK-5 receptor activity.
- Showed that TGF-beta increases the association of MEK5 with phospho-ERK5 and MEF2C in PTEC.
- Observed inhibition of ERK5 activation by TGF-beta or EGF using the p38 inhibitor SB-202190.
Conclusions:
- TGF-beta activates the ERK5 signaling pathway in human PTEC via the ALK-5 receptor.
- The study identifies MEF2C as a downstream component in TGF-beta-induced ERK5 signaling.
- These findings reveal a novel role for ERK5 in TGF-beta-mediated cellular processes within PTEC.
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