# SRC and ERK Regulate the Turnover of Cytoskeletal Keratin Filaments

## TL;DR

This study shows that the proteins SRC and ERK control how keratin filaments in epithelial cells break down and reorganize, which is important for cell function and response to signals.

## Contribution

The study identifies SRC and ERK as key regulators of keratin filament turnover, extending beyond EGF signaling.

## Key findings

- SRC and ERK kinases regulate keratin filament turnover in epithelial cells.
- PI3K/AKT and FAK have little to no effect on keratin filament turnover.
- SRC and ERK are activated by multiple signals and stresses, not just EGF.

## Abstract

Epithelial differentiation and function are tightly coupled to the keratin intermediate filament cytoskeleton. Keratin filaments are unique among the cytoskeletal filament systems in terms of biochemical properties, diversity and turnover mechanisms supporting epithelial plasticity in response to a multitude of environmental cues. Epidermal growth factor (EGF) is such a cue. It is not only intricately intertwined with epithelial physiology but also modulates keratin filament network organization by increasing keratin filament turnover. The involved EGF receptor (EGFR)-dependent intracellular signaling cascades, however, have not been identified to date. We therefore tested the effect of selective inhibitors of downstream effectors of the EGFR on keratin filament turnover using quantitative fluorescence recovery after photobleaching experiments as readouts. We find that SRC and ERK kinases are involved in the regulation of keratin filament turnover, whereas PI3K/AKT and FAK have little or no effect. The identification of SRC and ERK as major keratin filament regulators extends beyond EGF signaling since they are also activated by other signals and stresses. Our data unveil a mechanism that allows modification of the properties of keratin filaments at very high temporal and spatial acuity.