Integrin Activation and Matrix Binding Mediate Cellular Responses to Mechanical Stretch

• Published in: The Journal of biological chemistry Vol. 280; no. 17; pp. 16546 - 16549
• Main Authors: Katsumi, Akira, Naoe, Tomoki, Matsushita, Tadashi, Kaibuchi, Kozo, Schwartz, Martin Alexander
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 29-04-2005; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Cell Adhesion; Enzyme Activation; Enzyme Inhibitors - pharmacology; Extracellular Matrix - metabolism; Extracellular Signal-Regulated MAP Kinases - metabolism; Integrin alphaVbeta3 - metabolism; Integrins - chemistry; Integrins - metabolism; JNK Mitogen-Activated Protein Kinases - metabolism; Ligands; MAP Kinase Kinase 4; Mice; Mitogen-Activated Protein Kinase Kinases - metabolism; NIH 3T3 Cells; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Protein Conformation; Signal Transduction; Stress, Mechanical; Time Factors
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.C400455200

Mechanical tension is a critical determinant of cell growth, differentiation, apoptosis, migration, and development. Integrins have been implicated in sensing force but little is known about how forces are transduced to biochemical signals. We now show that mechanical strain stimulates conformational activation of integrin αvβ3 in NIH3T3 cells. Integrin activation is mediated by phosphoinositol 3-kinase and is followed by an increase in integrin binding to extracellular matrix proteins. Mechanical stretch stimulation of JNK was dependent on new integrin binding to extracellular matrix. These data define a molecular mechanism for the role of integrins in mechanotransduction.