Apoptosis Signal-regulating Kinase 1 (ASK1) Induces Neuronal Differentiation and Survival of PC12 Cells

摘要: Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein that activates the c-Jun N-terminal (JNK) and p38 signaling cascades. We report here expression of constitutively active ASK1 (ASK1ΔN) induces neurite outgrowth in rat pheochromocytoma cell line PC12. found to lesser extent JNK, but not ERK, were activated by ASK1ΔN PC12 cells. ASK1ΔN-induced was strongly inhibited treatment with inhibitor SB203580 MEK inhibitors, suggesting activation p38, rather than required for neurite-inducing activity also observed induced several neuron-specific proteins phosphorylation neurofilament proteins, confirming cells differentiated into mature neuronal ASK1. Moreover, ASK1ΔN-expressing survived serum-starved condition. thus appears mediate signals leading both differentiation survival Together previous reports indicating functions as pro-apoptotic intermediate, these results suggest has broad range biological activities depending on types and/or cellular context.