Effect of a tyrosine 155 to phenylalanine mutation of protein kinase Cδ on the proliferative and tumorigenic properties of NIH 3T3 fibroblasts

Tyrosine phosphorylation has emerged as an important mechanism in the regulation of enzyme function. In this paper, we describe a mutant of PKC delta altered at a single tyrosine residue which has the opposite effect compared with mild-type PKC delta on the growth characteristics of NIH 3T3 cells. Overexpression of wild-type PKC delta results in a decreased growth rate and a lower cell density at confluency. On the other hand, overexpression of PKC delta 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 delta, 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.