Mechanical control of cyclic AMP signalling and gene transcription through integrins.
This study was carried out to discriminate between two alternative hypotheses as to how cells sense mechanical forces and transduce them into changes in gene transcription. Do cells sense mechanical signals through generalized membrane distortion or through specific transmembrane receptors, such as integrins? Here we show that mechanical stresses applied to the cell surface alter the cyclic AMP signalling cascade and downstream gene transcription by modulating local release of signals generated by activated integrin receptors in a G-protein-dependent manner, whereas distortion of integrins in the absence of receptor occupancy has no effect.
Meyer
C J
CJ
Departments of Pathology and Surgery, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Alenghat
F J
FJ
Rim
P
P
Fong
J H
JH
Fabry
B
B
Ingber
D E
DE
D016475:3T3 Cells; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology; D005786:Gene Expression Regulation; D019012:Integrin beta1 / Q000378:metabolism*; D051379:Mice; D010812:Physical Stimulation; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic
D017362:Cyclic AMP Response Element-Binding Protein; D019012:Integrin beta1; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases