Carcinogenesis, Vol. 21, No. 5, 887-891,
May 2000
© 2000 Oxford University Press
Cancer Biology |
Effect of a tyrosine 155 to phenylalanine mutation of protein kinase C
on the proliferative and tumorigenic properties of NIH 3T3 fibroblasts
Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda, MD 20892 and
1 Department of Pharmacology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
Tyrosine phosphorylation has emerged as an important mechanism in the regulation of enzyme function. In this paper, we describe a mutant of PKC
altered at a single tyrosine residue which has the opposite effect compared with wild-type PKC on the growth characteristics of NIH 3T3 cells. Overexpression of wild-type PKC results in a decreased growth rate and a lower cell density at confluency. On the other hand, overexpression of PKC with a mutation from tyrosine to phenylalanine at position 155 results in a significantly higher rate of growth and a higher density at confluency compared with vector controls. Moreover, these cells are able to grow in soft agar and to form tumors in nude mice. In contrast to kinase negative PKC constructs, this mutant maintains in vitro kinase activity and shows a subcellular localization and a translocation pattern that are similar to those of the wild-type PKC. Whether the altered biological effect is due to the missing phosphorylation on tyrosine or the mutation from tyrosine to phenylalanine per se remains under investigation.
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