Back to Search
Start Over
Inhibition of RhoA and mTORC2/Rictor by Fingolimod (FTY720) induces p21-activated kinase 1, PAK-1 and amplifies podosomes in mouse peritoneal macrophages.
- Source :
-
Immunobiology . Nov2018, Vol. 223 Issue 11, p634-647. 14p. - Publication Year :
- 2018
-
Abstract
- Abstract Macrophage functions in the immune response depend on their ability to infiltrate tissues and organs. The penetration between and within the tissues requires degradation of extracellular matrix (ECM), a function performed by the specialized, endopeptidase- and actin filament- rich organelles located at the ventral surface of macrophage, called the podosomes. Podosome formation requires local inhibition of small GTPase RhoA activity, and depends on Rac 1/Rho guanine nucleotide exchange factor 7, β-PIX and its binding partner the p21-activated kinase (PAK-1). The activity of RhoA and Rac 1 is in turn regulated by mTOR/mTORC2 pathway. Here we showed that a fungus metabolite Fingolimod (FTY720, Gilenya), which is clinically approved for the treatment of multiple sclerosis, down-regulates Rictor, which is a signature molecule of mTORC2 and dictates its substrate (actin cytoskeleton) specificity, down-regulates RhoA, up-regulates PAK-1, and causes amplification of podosomes in mouse peritoneal macrophages. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01712985
- Volume :
- 223
- Issue :
- 11
- Database :
- Academic Search Index
- Journal :
- Immunobiology
- Publication Type :
- Academic Journal
- Accession number :
- 131514064
- Full Text :
- https://doi.org/10.1016/j.imbio.2018.07.009