Stimulus-specific activation and actin dependency of distinct, spatially separated ERK1/2 fractions in A7r5 smooth muscle cells.

PloS One
Susanne VetterkindKathleen G Morgan

Abstract

A proliferative response of smooth muscle cells to activation of extracellular signal regulated kinases 1 and 2 (ERK1/2) has been linked to cardiovascular disease. In fully differentiated smooth muscle, however, ERK1/2 activation can also regulate contraction. Here, we use A7r5 smooth muscle cells, stimulated with 12-deoxyphorbol 13-isobutylate 20-acetate (DPBA) to induce cytoskeletal remodeling or fetal calf serum (FCS) to induce proliferation, to identify factors that determine the outcomes of ERK1/2 activation in smooth muscle. Knock down experiments, immunoprecipitation and proximity ligation assays show that the ERK1/2 scaffold caveolin-1 mediates ERK1/2 activation in response to DPBA, but not FCS, and that ERK1/2 is released from caveolin-1 upon DPBA, but not FCS, stimulation. Conversely, ERK1/2 associated with the actin cytoskeleton is significantly reduced after FCS, but not DPBA stimulation, as determined by Triton X fractionation. Furthermore, cytochalasin treatment inhibits DPBA, but not FCS-induced ERK1/2 phosphorylation, indicating that the actin cytoskeleton is not only a target but also is required for ERK1/2 activation. Our results show that (1) at least two ERK1/2 fractions are regulated separately by specific ...Continue Reading

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Citations

Apr 30, 2013·PloS One·Robert J SaphirsteinKathleen G Morgan
Aug 31, 2013·Cell Communication and Signaling : CCS·Susanne VetterkindKathleen G Morgan
Jan 1, 2015·EMBO Reports·Hiroaki HirataMasahiro Sokabe

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Methods Mentioned

BETA
nuclear translocation
FCS
fluorescence microscopy
transfection
proximity ligation
immunoprecipitation
co-immunoprecipitation

Software Mentioned

Photoshop
Odyssey
NIS Elements AR

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