Integrin activation and matrix binding mediate cellular responses to mechanical stretch.
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 alphavbeta3 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.
Katsumi
Akira
A
Cardiovascular Research Center, Departments of Microbiology and Biomedical Engineering, Mellon Prostate Research Institute, University of Virginia, Charlottesville, Virginia 22908, USA.
Naoe
Tomoki
T
Matsushita
Tadashi
T
Kaibuchi
Kozo
K
Schwartz
Martin Alexander
MA
D000818:Animals; D002448:Cell Adhesion; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D016023:Integrins / Q000737:chemistry / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008024:Ligands; D048670:MAP Kinase Kinase 4; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D041681:NIH 3T3 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011487:Protein Conformation; D015398:Signal Transduction; D013314:Stress, Mechanical; D013997:Time Factors
D004791:Enzyme Inhibitors; D039302:Integrin alphaVbeta3; D016023:Integrins; D008024:Ligands; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases