p21-activated Protein Kinase γ-PAK Suppresses Programmed Cell Death of BALB3T3 Fibroblasts*

By R. Jakobi, E. Moertl, M. A. Koeppel. Journal of Biological Chemistry, 2001

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In response to stress stimulants, cells activate opposing signaling pathways for cell survival and programmed cell death. p21-activated protein kinase γ-PAK is involved in both cell survival and cell death pathways. Many stress stimulants activate γ-PAK as a full-length enzyme and as a proteolytic fragment. Caspase-mediated proteolytic activation parallels cell death and appears to be a pro-apoptotic factor in stress-induced cell death. Here, we show that activation of full-length γ-PAK promotes cell survival and suppresses stress-induced cell death. Expression of constitutively active γ-PAK-T402E, which mimics activated full-length γ-PAK, stimulates cell survival of BALB3T3 fibroblasts in response to tumor necrosis factor α, growth factor withdrawal, and UVC light. This stimulation of cell survival is mainly due to protection of cells from cell death rather than by stimulation of proliferation. Expression of γ-PAK-T402E increases phosphorylation of the pro-apoptotic Bcl-2 family protein Bad and protects from cell death induced by ectopic expression of Bad. In response to tumor necrosis factor α, expression of γ-PAK-T402E increases the early but reduces the late activation of ERK, JNK, and p38. Our results indicate that the ubiquitous γ-PAK may have a crucial function in cell survival by regulating the pro-apoptotic activity of Bad and the stress-induced activation of ERK, JNK, and p38 pathways.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/9e402523b361622721b9b74cefd5ae4a28b3de56

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