%0 Journal Article
%T Caspase Activation of p21-Activated Kinase 2 Occurs During Cisplatin-Induced Apoptosis of SH-SY5Y Neuroblastoma Cells and in SH-SY5Y Cell Culture Models of Alzheimer¡¯s and Parkinson¡¯s Disease
%A Jerry W. Marlin
%A Yu-Wen E. Chang and Rolf Jakobi
%J Journal of Cell Death
%D 2012
%I 
%R 10.4137/JCD.S4611
%X p21-activated kinase 2 (PAK-2) appears to have a dual function in the regulation of cell survival and cell death. Activation of full-length PAK-2 by the p21 G-proteins Rac or Cdc42 stimulates cell survival. However, PAK-2 is unique among the PAK family because it is also activated through proteolytic cleavage by caspase 3 or similar caspases to generate the constitutively active PAK-2p34 fragment. Caspase activation of PAK-2 correlates with the induction of apoptosis in response to many stimuli and recombinant expression of PAK-2p34 has been shown to stimulate apoptosis in several human cell lines. Here, we show that caspase activation of PAK-2 also occurs during cisplatin-induced apoptosis of SH-SY5Y neuroblastoma cells as well as in SH-SY5Y cell culture models for Alzheimer¡¯s and Parkinson¡¯s disease. Inhibition of mitochondrial complex I or of ubiquitin/proteasome-mediated protein degradation, which both appear to be involved in Parkinson¡¯s disease, induce apoptosis and caspase activation of PAK-2 in SH-SY5Y cells. Overexpression of the amyloid precursor protein, which results in accumulation and aggregation of ¦Â-amyloid peptide, the main component of ¦Â-amyloid plaques in Alzheimer¡¯s disease, also induces apoptosis and caspase activation of PAK-2 in SH-SY5Y cells. Expression of the PAK-2 regulatory domain inhibits caspase-activated PAK-2p34 and prevents apoptosis in 293T human embryonic kidney cells, indicating that caspase activation of PAK-2 is directly involved in the apoptotic response. This is the first evidence that caspase activation of PAK-2 correlates with apoptosis in cell culture models of Alzheimer¡¯s and Parkinson¡¯s disease and that selective inhibition of caspase-activated PAK-2p34 could prevent apoptosis.
%U http://www.la-press.com/caspase-activation-of-p21-activated-kinase-2-occurs-during--cisplatin--article-a2021