Physiological stress and nerve growth factor treatment regulate stress-activated protein kinase activity in PC12 cells.
The stress-activated protein kinases (SAPKs) are differentially activated by a variety of cellular stressors in PC12 cells. SAPK activation has been linked to the induction of apoptotic cell death upon serum withdrawal from undifferentiated cells or following nerve growth factor (NGF) withdrawal of neuronally differentiated PC12 cells. However, withdrawal of trophic support from differentiated cells led to only a very modest elevation of SAPK activity and led us to investigate the basis of the relative insensitivity of these enzymes to stressors. NGF-stimulated differentiation of the cells resulted in the elevation of basal SAPK activity to levels four- to sevenfold greater than in untreated cells, which was correlated with an approximate fivefold increase in SAPK protein levels. Paradoxically, in NGF-differentiated PC12 cells, exposure to cellular stressors provoked a proportionately smaller stimulation of SAPK activity than that observed in naive cells, despite the presence of much higher levels of SAPK protein. The insensitivity of SAPK to activation by stressors was reflective of the activity of the SAPK activator SEK, whose activation was also diminished following NGF differentiation of the cells. The data demonstrate that SAPKs are subject to complex controls through both induction of SAPK expression and the regulation mediated by upstream elements within this pathway.
Goodman
M N
MN
Department of Neurology, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4928, USA.
Reigh
C W
CW
Landreth
G E
GE
D000818:Animals; D015153:Blotting, Western; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000502:physiology; D016895:Culture Media, Serum-Free; D006358:Hot Temperature; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D051381:Rats; D013268:Stimulation, Chemical; D013312:Stress, Physiological / Q000201:enzymology*
D016895:Culture Media, Serum-Free; D009414:Nerve Growth Factors; D016755:Proto-Oncogene Proteins c-jun; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases