Downregulation of HD-PTP by high magnesium concentration: novel insights into magnesium-induced endothelial migration.
Magnesium promotes endothelial migration, an event which is orchestrated by a complex interplay between protein tyrosine kinases and phosphatases. We found that high extracellular concentrations of magnesium do not modulate the levels and the activation of FAK and Src, two tyrosine kinases involved in driving cell migration. Interestingly, we show that magnesium induced-endothelial motility correlates with the downregulation of HD-PTP, a potential tyrosine phopshatase previously shown to be involved in modulating cell migration. The decreased amounts of HD-PTP are not dependent upon transcriptional mechanisms. In contrast to Fibroblast Growth Factor-induced HD-PTP downregulation, the proteasome seems not to be involved in regulating HD-PTP levels in endothelial cells cultured in high magnesium containing medium. Our results indicate that, in the presence of high magnesium concentrations, endothelial cells are stimulated to migrate through complex mechanisms involving also HD-PTP.
Leidi
Marzia
M
Dipartimento di Scienze Cliniche Luigi Sacco, Università di Milano, Milano, Italy.
Baldoli
Erika
E
Maier
Jeanette Am
JA
D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects*; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D008274:Magnesium / Q000494:pharmacology*; D010766:Phosphorylation; D054558:Protein Tyrosine Phosphatases, Non-Receptor / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000166:cytology; D019061:src-Family Kinases / Q000378:metabolism
D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases; C114102:PTPN23 protein, human; D054558:Protein Tyrosine Phosphatases, Non-Receptor; D008274:Magnesium