20500 h o , Finland (1.H.I SH-SY5Y human neuroblastoma cells can be induced to differentiate into a neuronal phenotype by treatment with 12-O-tetradecanoylphorbol-13-acctatc UPA). In other cell systems, TPA treatment frequently leads to down-regulation of protein kinase C (PKC). However, we now rep
Protein kinase C-α and -ε are enriched in growth cones of differentiating SH-SY5Y human neuroblastoma cells
✍ Scribed by V. Parrow; S. Fagerström; G. Meyerson; E. Nånberg; S. Påhlman
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 989 KB
- Volume
- 41
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
SH-SYSY cells differentiate into neuronal-like cells and express marker proteins like growth-associated protein (GAP-43) and neuropeptide tyrosine when treated with a low concentration (16 nM) of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) in the presence of growth factors or serum. Both control and differentiated cells expressed protein kinase C-w (PKC-w), PKC-&, and PKC-I; as revealed by Western blot analyses, but the subcellular distribution of the three isoforms was not uniform, indicating specific localized functions of the enzymes. In growth cones prepared from differentiating cells PKC-w and PKC-E were enriched. In contrast, PKC-I; was more evenly distributed within the differentiating cell. Cells treated with a high concentration of TPA (1.6 FM) differentiate poorly and continue to proliferate. In those cells, PKC-a and PKC-E were found to be down-regulated while PKC-I; remained present. Thus, down-regulation of PKC-a and PKC-E appears to be incompatible with neuronal differentiation of SH-SYSY cells. These cells also differentiate when treated with a combination of basic fibroblast growth factor and insulin-like growth factor I. Growth cones isolated from such cells are also enriched in PKC-a and PKC-E, but not in PKC-1;. Based on the subcellular distribution of PKC-a and E, and that PKC substrates like GAP-43 and pp6OC-"" are enriched in SH-SYSY growth cones, a role during neurite growth is suggested.
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