Mechanotransduction through growth-factor shedding into the extracellular space

Tschumperlin, Daniel J.; Dai, Guohao; Maly, Ivan V.; Kikuchi, Taisuke; Laiho, Lily H.; McVittie, Anna K.; Haley, Kathleen J.; Lilly, Craig M.; So, Peter T. C.; Lauffenburger, Douglas A.; Kamm, Roger D.; Drazen, Jeffrey M.

doi:10.1038/nature02543

Cited by 317 publications

(331 citation statements)

References 31 publications

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“…For specialized mechanoreceptors in the body, ion channels and their anchors are the common features of these mechanosensors (13). For "non-specialized" cells, searching for mechanosensors has also been focused on cellular membrane proteins such as stretch-activated ion channels (16,17), integrins (2,8), and growth factor receptors (19). It has been recently reported that a Z-disc complex in cardiomyocytes could sense mechanical stretch in the heart (36).…”

Section: Discussionmentioning

confidence: 99%

“…There is increasing evidence to support the belief that integrins are mechanosensors (2,8), but how physical forces are converted into biochemical signals through the ECM-integrin-cytoskeleton complex is not addressed by this model system. Recently, Tschumperlin et al reported that compressive stress shrinks the lateral intercellular space surrounding epithelial cells and triggers cellular signaling via autocrine binding of epidermal growth factor (EGF) family ligands to the EGF receptor (19). This observation again supports the importance of cellular membrane proteins in mechanosensory processes.…”

mentioning

confidence: 84%

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Conversion of Mechanical Force into Biochemical Signaling

Han

Bai

Lodyga

et al. 2004

Journal of Biological Chemistry

142

132

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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 proteinprotein interaction via specific binding sites may represent a novel intracellular mechanism for cells to sense mechanical stimulation.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 84%

Conversion of Mechanical Force into Biochemical Signaling

Han

Bai

Lodyga

et al. 2004

Journal of Biological Chemistry

142

132

View full text Add to dashboard Cite

show abstract

“…Though originally described as the receptor for EGF, more recent data have demonstrated EGFR activation by other extracellular ligands (TGF␣, amphiregulin, epiregulin, HBEGF, betacellulin). These transmembrane proligands are cleaved and released into the extracellular milieu by matrix metalloproteases (a disintegrin and metalloproteinase family (ADAMs)) leading to activation of EGFR (13)(14)(15)(16). EGFR can also be activated by a still undetermined oxidant-dependent intracellular transactivation from other receptors (17,18).…”

Section: Respiratory Syncytial Virus (Rsv)mentioning

confidence: 99%

Activation of the Epidermal Growth Factor Receptor by Respiratory Syncytial Virus Results in Increased Inflammation and Delayed Apoptosis

Monick

Cameron

Staber

et al. 2005

Journal of Biological Chemistry

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“…activation (25). Our previous study has implicated the matrix receptor dystroglycan as an important regulator of the response of AEC to mechanical stimulation in vitro (7).…”

Section: Discussionmentioning

confidence: 99%

Stretch-Induced Activation of AMP Kinase in the Lung Requires Dystroglycan

Budinger¹,

Urich²,

DeBiase³

et al. 2008

Am J Respir Cell Mol Biol

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Lung cells are exposed to cyclic stretch during normal respiration and during positive pressure mechanical ventilation administered to support gas exchange. Dystroglycan is a ubiquitously expressed matrix receptor that is required for normal basement membrane formation during embryogenesis and for maintaining the function of skeletal muscle myocytes and neurons where it links cells to matrix. We previously reported that equibiaxial stretch of primary alveolar epithelial cells activated the MAP kinase pathway ERK1/2 through a mechanism that required an interaction between dystroglycan and matrix. We determined whether this mechanism of mechanotransduction activates other signaling cascades in lung epithelium. Exposure of rat epithelial alveolar type II cells (AEC) to cyclic mechanical stretch resulted in activation of 59 AMP-activated protein kinase (AMPK). This response was not affected by pretreatment of AEC with the ERK inhibitor PD98059 but was inhibited by knockdown in dystroglycan expression. Moreover, production of reactive oxygen species was enhanced in mechanically stimulated AEC in which dystroglycan was knocked down. This enhancement was reversed by treatment of AEC with an AMPK activator. Activation of AMPK was also observed in lung homogenates from mice after 15 minutes of noninjurious mechanical ventilation. Furthermore, knockdown of dystroglycan in the lungs of mice using an adenovirus encoding a dystroglycan shRNA prevented the stretch-induced activation of AMPK. These results suggest that exposure to cyclic stretch activates the metabolic sensing pathway AMPK in the lung epithelium and supports a novel role for dystroglycan in this mechanotransduction.

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Mechanotransduction through growth-factor shedding into the extracellular space

Cited by 317 publications

References 31 publications

Conversion of Mechanical Force into Biochemical Signaling

Conversion of Mechanical Force into Biochemical Signaling

Activation of the Epidermal Growth Factor Receptor by Respiratory Syncytial Virus Results in Increased Inflammation and Delayed Apoptosis

Stretch-Induced Activation of AMP Kinase in the Lung Requires Dystroglycan

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