Protein Kinase A activity is regulated by actomyosin contractility during cell migration and is required for durotaxis
| Autor: | Alan K. Howe, Andrew J. McKenzie, Tamara F. Williams, Kathryn V Svec |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Myosin light-chain kinase
Myosin ATPase Motility Myosins Biology Mechanotransduction Cellular Extracellular matrix 03 medical and health sciences Contractile Proteins 0302 clinical medicine Cell Movement Cell Line Tumor Myosin Humans Phosphorylation Kinase activity Protein kinase A Molecular Biology Rho-associated protein kinase 030304 developmental biology rho-Associated Kinases 0303 health sciences Durotaxis Chemistry Cell migration Actomyosin Articles Cell Biology Cyclic AMP-Dependent Protein Kinases Extracellular Matrix Cell biology Actin Cytoskeleton Cell Motility 030220 oncology & carcinogenesis Female 030217 neurology & neurosurgery Muscle Contraction |
| Zdroj: | Molecular Biology of the Cell |
| DOI: | 10.1101/392399 |
| Popis: | Dynamic subcellular regulation of Protein kinase A (PKA) activity is important for the motile behavior of many cell types, yet the mechanisms governing PKA activity during cell migration remain largely unknown. The motility of SKOV-3 epithelial ovarian cancer (EOC) cells has been shown to be dependent on both localized PKA activity and, more recently, on mechanical reciprocity between cellular tension and extracellular matrix (ECM) rigidity. Here, we investigated the possibility that PKA is regulated by mechanical signaling during migration. We find that localized PKA activity in migrating cells rapidly decreases upon inhibition of actomyosin contractility (specifically, of myosin ATPase, ROCK (Rho kinase), or MLCK (myosin light chain kinase) activity). Moreover, PKA activity is spatially and temporally correlated with cellular traction forces in migrating cells. Additionally, PKA is rapidly and locally activated by mechanical stretch in an actomyosin contractility-dependent manner. Finally, inhibition of PKA activity inhibits mechanically-guided migration, also known as durotaxis. These observations establish PKA as a locally-regulated effector of cellular mechanotransduction and as a regulator of mechanically-guided cell migration. |
| Databáze: | OpenAIRE |
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