Title

Focal adhesion kinase is involved in mechanosensing during fibroblast migration

UMMS Affiliation

Department of Physiology

Date

9-27-2001

Document Type

Article

Subjects

Animals; Cell Adhesion; Cell Movement; Cells, Cultured; Embryo, Mammalian; Fibroblasts; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; Focal Adhesions; Green Fluorescent Proteins; Luminescent Proteins; Metalloproteins; Mice; Protein-Tyrosine Kinases; Recombinant Fusion Proteins; Tetracycline; Transfection

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

Focal adhesion kinase (FAK) is a non-receptor protein tyrosine kinase localized at focal adhesions and is believed to mediate adhesion-stimulated effects. Although ablation of FAK impairs cell movement, it is not clear whether FAK might be involved in the guidance of cell migration, a role consistent with its putative regulatory function. We have transfected FAK-null fibroblasts with FAK gene under the control of the tetracycline repression system. Cells were cultured on flexible polyacrylamide substrates for the detection of traction forces and the application of mechanical stimulation. Compared with control cells expressing wild-type FAK, FAK-null cells showed a decrease in migration speed and directional persistence. In addition, whereas FAK-expressing cells responded to exerted forces by reorienting their movements and forming prominent focal adhesions, FAK-null cells failed to show such responses. Furthermore, FAK-null cells showed impaired responses to decreases in substrate flexibility, which causes control cells to generate weaker traction forces and migrate away from soft substrates. Cells expressing Y397F FAK, which cannot be phosphorylated at a key tyrosine site, showed similar defects in migration pattern and force-induced reorientation as did FAK-null cells. However, other aspects of F397-FAK cells, including the responses to substrate flexibility and the amplification of focal adhesions upon mechanical stimulation, were similar to that of control cells. Our results suggest that FAK plays an important role in the response of migrating cells to mechanical input. In addition, phosphorylation at Tyr-397 is required for some, but not all, of the functions of FAK in cell migration.

Rights and Permissions

Citation: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11295-300. Link to article on publisher's site

DOI of Published Version

10.1073/pnas.201201198

Related Resources

Link to Article in PubMed

Journal Title

Proceedings of the National Academy of Sciences of the United States of America

PubMed ID

11572981