Type II cyclic guanosine monophosphate-dependent protein kinase inhibits Rac1 activation in gastric cancer cells

摘要: Enhanced motility of cancer cells is a critical step in promoting tumor metastasis, which remains the major cause gastric cancer-associated mortality. The small GTPase Rac1 key signaling component regulation cell migration. Previous studies have demonstrated that activity may be regulated by protein kinase G (PKG); however, underlying mechanism not yet clear. current study aimed to investigate effect type II cyclic guanosine monophosphate (cGMP)-dependent (PKG II) on activity. human line AGS was infected with adenoviral constructs encoding PKG increase expression this enzyme, and treated cGMP analog (8-pCPT-cGMP) induce its activation. A Transwell assay employed measure migration, assessed using pull-down assay. Immunoprecipitation used isolate protein. Phosphorylation phosphatidylinositol 4,5 bisphosphate 3 (PI3K) downstream effecter B (Akt) are associated lysophosphatidic acid (LPA)-induced motility/migration cells. Extracellular signal (ERK) molecule Mitogen activated (MAPK) mediated pathway. ERK upstream activator MAPK (MEK) also involved LPA-induced PI3K/Akt, MEK/ERK enriched were detected western blotting. results revealed blocking activation ectopically expressing an inactive mutant (T17N) impeded Increased inhibited migration Rac1; it had no phosphorylation Rac1. PI3K/Akt signaling, important for These suggest affects LPA-stimulated activation, via inhibition signaling.