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Conversion of mechanical force into biochemical signaling
Bing Han1, Xiao-Hui Bai, Monika Lodyga
1Division of Cellular and Molecular Biology, Toronto General Research Institute, University Health Network, Toronto, Ontario M5G 2C4, Canada.
The Journal of Biological Chemistry
|October 16, 2004
Summary
Cells sense mechanical forces through the actin cytoskeleton. Actin filament-associated protein (AFAP) directly activates c-Src protein tyrosine kinase, converting physical stimuli into biochemical signals.
Area of Science:
- Cell Biology
- Biophysics
- Biochemistry
Background:
- Physical forces regulate crucial cellular processes like proliferation, differentiation, and apoptosis.
- The mechanisms by which cells perceive mechanical stimulation remain largely undefined.
- Current research often identifies cell membrane proteins as primary mechanosensors.
Purpose of the Study:
- To elucidate the intracellular mechanisms underlying cellular mechanosensation.
- To identify novel components involved in the transduction of mechanical signals into biochemical responses.
Main Methods:
- Investigated the role of actin filament-associated protein (AFAP) in mechanical stretch-induced signaling.
- Utilized site-directed mutagenesis to probe AFAP's interaction with c-Src.
- Examined c-Src protein tyrosine kinase activation in response to mechanical stress.
Main Results:
- Mechanical stretch activates c-Src protein tyrosine kinase via AFAP.
- AFAP directly binds to the Src homology 3 and/or 2 domains of c-Src.
- Mutating AFAP's binding sites abrogated mechanical stretch-induced c-Src activation.
Conclusions:
- The cytoskeleton transmits mechanical forces intracellularly.
- Interactions between cytoskeletal proteins and signal transduction enzymes convert physical forces into biochemical reactions.
- Cytoskeleton deformation-mediated protein-protein interactions represent a novel mechanism for cellular mechanosensation.