P. Acs et al., Effect of a tyrosine 155 to phenylalanine mutation of protein kinase C delta on the proliferative and tumorigenic properties of NIH 3T3 fibroblasts, CARCINOGENE, 21(5), 2000, pp. 887-891
Tyrosine phosphorylation has emerged as an important mechanism in the regul
ation 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. O
verexpression of wild-type PKC delta results in a decreased growth rate and
a lower cell density at confluency. On the other hand, overexpression of P
KC delta with a mutation from tyrosine to phenylalanine at position 155 res
ults in a significantly higher rate of growth and a higher density at confl
uency 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 negati
ve 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 tyrosi
ne to phenylalanine per se remains under investigation.