Enhanced cell cycle progression and down regulation of p21(Cip1/Waf1) by PRL tyrosine phosphatases.
Human PRL-1, PRL-2, and PRL-3 tyrosine phosphatases induce the malignant transformation of epithelial cells. We tested the hypothesis that the oncogenic effects of PRL occur by increasing cellular proliferation. Cells stably transfected with PRL-1 or PRL-2 exhibited 2.7-3.3-fold increases over control cells in the rate of DNA synthesis and the proportion of cells in S-phase, and they progressed more rapidly from G1 into S. In addition, cells overexpressing either PRL-1 or PRL-2 exhibited enhanced cyclin-dependent kinase 2 (CDK2) activity and significantly lower p21(Cip1/Waf1) protein levels, and PRL-1 overexpressing cells had higher cyclin A protein levels than control cells. We conclude that PRL phosphatases increase cell proliferation by stimulating progression from G1 into S phase, and this process may be dependent on the down regulation of the cyclin dependent kinase inhibitor p21(Cip1/Waf1).
Werner
Sean R
SR
Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202-5132, USA.
Lee
Paul A
PA
DeCamp
Matthew W
MW
Crowell
Dring N
DN
Randall
Stephen K
SK
Crowell
Pamela L
PL
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D042846:CDC2-CDC28 Kinases / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D006224:Cricetinae; D019925:Cyclin A / Q000502:physiology; D051357:Cyclin-Dependent Kinase 2; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000502:physiology*; D015536:Down-Regulation; D006801:Humans; D015151:Immunoblotting; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D017027:Protein Tyrosine Phosphatases / Q000502:physiology*; D014162:Transfection
C493956:CDKN1A protein, human; D019925:Cyclin A; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D017027:Protein Tyrosine Phosphatases