ABSTRACT

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 PAK1Δ15. PAK1Δ15 and PAK2 levels correlated with surface density of integrins β1 and αVβ3. 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.

摘要

P21激活的激酶（PAK）调节与细胞骨架动力学有关的过程。通过蛋白质和mRNA水平测量白血病细胞中PAK的表达。在功能测定中，我们分析了PAK抑制剂IPA-3和FRAX597对细胞粘附性和生存力的影响。PAK2在细胞系中占主导地位，而原代细胞也表达了相当数量的PAK1转录同工型：PAK1完整和PAK1Δ15。PAK1Δ15和PAK2水平与整联蛋白β1和αVβ3的表面密度相关。PAK1已满，但PAK2未出现在膜突起中。阻止PAK活化的IPA-3仅在半贴壁HEL细胞中诱导细胞收缩。抑制PAK激酶活性的FRAX597增加了所有白血病细胞的细胞表面接触面积。两种抑制剂均降低了细胞附着的稳定性并诱导了细胞死亡。