Group I p21-activated kinases in leukemia cell adhesion to fibronectin

P21-activated kinases (PAK) regulate processes associated with cytoskeleton dynamics. PAK expression in leukemia cells was measured on protein and mRNA levels. In functional assays, we analyzed the effect of PAK inhibitors IPA-3 and FRAX597 on cell adhesivity and viability. PAK2 was dominant in cell lines, whereas primary cells also expressed comparable amount of PAK1 transcription isoforms: PAK1-full and PAK1 Delta 15. PAK1 Delta 15 and PAK2 levels correlated with surface density of integrins beta 1 and alpha V beta 3. PAK1-full, but not PAK2, was present in membrane protrusions. IPA-3, which prevents PAK activation, induced cell contraction in semi-adherent HEL cells only. FRAX597, which inhibits PAK kinase activity, increased cell-surface contact area in all leukemia cells. Both inhibitors reduced the stability of cell attachment and induced cell death.

Automated summary

P21-activated kinases (PAK) regulate cytoskeleton dynamics, and their expression levels in leukemia cells were measured on both protein and mRNA levels. The different isoforms of PAK1 and PAK2 levels were correlated with the density of integrins on cell surface. Inhibitors targeting PAK showed different effects on cell adhesion and viability in leukemia cells.