Regulation of focal adhesion targeting and inhibitory functions of the FAK related protein FRNK using a novel estrogen receptor "switch"

Cell Motility and the Cytoskeleton
Karen H MartinJ Thomas Parsons

Abstract

Focal adhesion kinase (FAK) is a regulator of numerous adhesion-dependent processes including cell migration, cell proliferation, and cell survival. The C-terminal domain of FAK, FAK-related nonkinase (FRNK), is autonomously expressed and functions as an inhibitor of FAK signaling. Previous attempts to use FRNK as a tool to dissect FAK signaling have been limited because of an inability to temporally regulate the inhibitory functions of FRNK. In this report, we describe and characterize a conditionally targeted form of FRNK that was created by fusing the hormone-binding domain of the estrogen receptor (ER*) to the C-terminus of FRNK. In the absence of added hormone, FRNK-ER* was diffusely distributed throughout the cytoplasm of cells. Upon addition of hormone, the cytoplasmic pool of FRNK-ER* was rapidly redistributed to focal adhesions. We demonstrate that cells expressing FRNK-ER* show a hormone-dependent decrease in FAK tyrosine phosphorylation and cell migration. Furthermore, when cells expressing of FRNK-ER* were treated with hormone, the cells responded with a dramatic change in cell morphology, suggesting a role for FAK in the regulation of the adhesive properties of focal adhesions.

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Citations

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Feb 22, 2012·Journal of Cell Science·Yu LiuWen-Cheng Xiong
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Mar 18, 2003·Journal of Cell Science·J Thomas Parsons
Jul 15, 2009·Journal of Cell Science·Matthew W C ChanChristopher A McCulloch

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