Conversion of Mechanical Force into Biochemical Signaling

Physical forces play important roles in regulating cell proliferation, differentiation, and death by activating intracellular signal transduction pathways. How cells sense mechanical stimulation, however, is largely unknown. Most studies focus on cellular membrane proteins such as ion channels, inte...

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Bibliographic Details
Published in:The Journal of biological chemistry 2004-12, Vol.279 (52), p.54793-54801
Main Authors: Han, Bing, Bai, Xiao-Hui, Lodyga, Monika, Xu, Jing, Yang, Burton B., Keshavjee, Shaf, Post, Martin, Liu, Mingyao
Format: Article
Language:English
Subjects:
Animals
Binding Sites
Biomechanical Phenomena
Cell Line
Chickens
Chlorocebus aethiops
Cloning, Molecular
COS Cells
CSK Tyrosine-Protein Kinase
Cytoskeletal Proteins - physiology
Cytoskeleton - physiology
Cytoskeleton - ultrastructure
Enzyme Activation
Green Fluorescent Proteins - genetics
Humans
Mice
Microfilament Proteins - genetics
Microfilament Proteins - physiology
NIH 3T3 Cells
Protein-Tyrosine Kinases - chemistry
Protein-Tyrosine Kinases - metabolism
RNA, Small Interfering - pharmacology
Signal Transduction
src-Family Kinases
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Summary:Physical forces play important roles in regulating cell proliferation, differentiation, and death by activating intracellular signal transduction pathways. How cells sense mechanical stimulation, however, is largely unknown. Most studies focus on cellular membrane proteins such as ion channels, integrins, and receptors for growth factors as mechanosensory units. Here we show that mechanical stretch-induced c-Src protein tyrosine kinase activation is mediated through the actin filament-associated protein (AFAP). Distributed along the actin filaments, AFAP can directly active c-Src through binding to its Src homology 3 and/or 2 domains. Mutations at these specific binding sites on AFAP blocked mechanical stretch-induced c-Src activation. Therefore, mechanical force can be transmitted along the cytoskeleton, and interaction between cytoskeletal associated proteins and enzymes related to signal transduction may convert physical forces into biochemical reactions. Cytoskeleton deformation-induced protein-protein interaction via specific binding sites may represent a novel intracellular mechanism for cells to sense mechanical stimulation.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M406880200