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

Citation
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
Citations number
25
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
CARCINOGENESIS
ISSN journal
01433334 → ACNP
Volume
21
Issue
5
Year of publication
2000
Pages
887 - 891
Database
ISI
SICI code
0143-3334(200005)21:5<887:EOAT1T>2.0.ZU;2-I
Abstract
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.