This study demonstrates that the isolated regulatory (R) domain (amino acids 1 -270) of human protein kinase C a (PKCa) is a potent inhibitor of PKCP-I activity in a yeast expression system. The PKCa R domain fused to glutathione-S-transferase competitively inhibited the activity of yeast-expressed
Uneven distribution of protein kinase C-α and -β isozymes in human sarcomas and carcinomas
✍ Scribed by Antonio Cuadrado; Wolfgang Issing; Timothy P. Fleming; Christopher J. Molloy
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 842 KB
- Volume
- 159
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
Abstract
Protein kinase C (PKC) represents a family of structurally related Ser/Tre kinases which are involved in mitogenic signalling and may contribute to human neoplasia. To address this issue, the messenger RNA and protein levels of PKC isoenzymes α and β were analyzed in several human sarcoma‐ and carcinoma‐derived cell lines. Carcinomas contained low or undetectable levels of either PKC‐α or PKC‐β. Sarcomas exhibited similar or increased PKC expression compared to human diploid fibroblasts. Moreover, sarcoma cell lines expressing one PKC isoform did not contain detectable levels of the other. When PKC was depleted from the tumor cells, we observed that the PKC overexpressing sarcomas had reduced their malignant properties as determined by their ability to grow in semisolid medium. In addition, epidermal growth factor‐stimulated and erbB2‐transformed fibroblasts exhibited enhanced cell growth in the absence of PKC. We propose a model for the effect of PKC as a negative regulator of proliferation in epithelial cells and a growth promoter in fibroblasts. © 1994 wiley‐Liss, Inc.
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