Focal adhesion kinase modulates tension signaling to control actin and focal adhesion dynamics

M Schober, S Raghavan, M Nikolova, L Polak… - The Journal of cell …, 2007 - rupress.org
M Schober, S Raghavan, M Nikolova, L Polak, HA Pasolli, HE Beggs, LF Reichardt, E Fuchs
The Journal of cell biology, 2007rupress.org
In response to αβ1 integrin signaling, transducers such as focal adhesion kinase (FAK)
become activated, relaying to specific machineries and triggering distinct cellular responses.
By conditionally ablating Fak in skin epidermis and culturing Fak-null keratinocytes, we
show that FAK is dispensable for epidermal adhesion and basement membrane assembly,
both of which require αβ1 integrins. FAK is also dispensible for proliferation/survival in
enriched medium. In contrast, FAK functions downstream of αβ1 integrin in regulating …
In response to αβ1 integrin signaling, transducers such as focal adhesion kinase (FAK) become activated, relaying to specific machineries and triggering distinct cellular responses. By conditionally ablating Fak in skin epidermis and culturing Fak-null keratinocytes, we show that FAK is dispensable for epidermal adhesion and basement membrane assembly, both of which require αβ1 integrins. FAK is also dispensible for proliferation/survival in enriched medium. In contrast, FAK functions downstream of αβ1 integrin in regulating cytoskeletal dynamics and orchestrating polarized keratinocyte migration out of epidermal explants. Fak-null keratinocytes display an aberrant actin cytoskeleton, which is tightly associated with robust, peripheral focal adhesions and microtubules. We find that without FAK, Src, p190RhoGAP, and PKL–PIX–PAK, localization and/or activation at focal adhesions are impaired, leading to elevated Rho activity, phosphorylation of myosin light chain kinase, and enhanced tensile stress fibers. We show that, together, these FAK-dependent activities are critical to control the turnover of focal adhesions, which is perturbed in the absence of FAK.
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