Protein kinase C isoforms and growth, differentiation and phosphatidylcholine turnover in human neuroblastoma cells.

Neuroblastoma and glioma cells differentially express isoforms of protein kinase C (PKC) and myristoylated PKC substrates (e.g. MARCKS). Correlation with metabolism of membrane phospholipids suggests that PKC-alpha and MARCKS may be required to mediate phosphatidylcholine turnover stimulated by phorbol ester (beta-TPA). To evaluate relationships to neural cell differentiation, SK-N-SH human neuroblastoma cells were treated with 20 nM beta-TPA. In beta-TPA-treated cells, growth arrest and differentiation occurred (neurite extension; 40-60% decrease in cell number, total protein and RNA). By day 4, mRNA for PKC-alpha and MARCKS increased and, after an initial decrease, PKC-alpha protein also increased. At day 4, phosphatidylcholine synthesis was 3-5 fold greater than in control cells. In contrast, C6 glioma cells treated with beta-TPA showed no growth arrest, decreased PKC-alpha protein (< 20%) and lower phosphatidylcholine synthesis. Thus, induced differentiation of human neuroblastoma cells involved increased expression of PKC-alpha and MARCKS and synthesis of phosphatidylcholine, consistent with involvement of PKC-alpha and MARCKS in regulation of phosphatidylcholine turnover during neurite growth.