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

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
Kateřina Kuželová, Adam Obr, Pavla Röselová, Dana Grebeňová, Petra Otevřelová, Barbora Brodská, Aleš Holoubek
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引用次数: 6

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.

Abstract Image

Abstract Image

Abstract Image

I组p21活化激酶在白血病细胞对纤维连接蛋白粘附中的作用。
p21活化激酶(PAK)调节与细胞骨架动力学相关的过程。检测PAK在白血病细胞中的蛋白和mRNA表达水平。在功能实验中,我们分析了PAK抑制剂IPA-3和FRAX597对细胞粘附性和活力的影响。PAK2在细胞系中占主导地位,而原代细胞也表达相当数量的PAK1转录异构体:PAK1-full和PAK1Δ15。PAK1Δ15和PAK2水平与整合素β1和αVβ3表面密度相关。膜突中pak1表达丰富,PAK2不表达。IPA-3抑制PAK活化,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。这两种抑制剂都降低了细胞附着的稳定性并诱导细胞死亡。
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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