REGULATION OF FRA-1 AND FRA-2 PHOSPHORYLATION DIFFERS DURING THE CELL-CYCLE OF FIBROBLASTS AND PHOSPHORYLATION IN-VITRO BY MAP KINASE AFFECTS DNA-BINDING ACTIVITY

Citation
Mc. Gruda et al., REGULATION OF FRA-1 AND FRA-2 PHOSPHORYLATION DIFFERS DURING THE CELL-CYCLE OF FIBROBLASTS AND PHOSPHORYLATION IN-VITRO BY MAP KINASE AFFECTS DNA-BINDING ACTIVITY, Oncogene, 9(9), 1994, pp. 2537-2547
Citations number
67
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Genetics & Heredity",Oncology
Journal title
ISSN journal
0950-9232
Volume
9
Issue
9
Year of publication
1994
Pages
2537 - 2547
Database
ISI
SICI code
0950-9232(1994)9:9<2537:ROFAFP>2.0.ZU;2-W
Abstract
The Fos family of transcription factors, c-Fos, FosB, Fra-1 and Fra-2, are rapidly induced in quiescent fibroblasts following serum or growt h factor stimulation. The Fos proteins show distinct patterns of expre ssion during cell growth with only Fra-1 and Fra-2 maintained at signi ficant levels in growing cells, suggesting that the different family m embers direct unique functions for cell growth. Post-translational mod ification of Fos proteins has been observed following serum stimulatio n, which may allow an additional level of regulation. Our studies show that the synthesis and post-translational modification of Fra-1 and F ra-2 in Swiss 3T3 cells is serum-dependent during G(1) following the t ransition from G(0) and during asynchronous growth but is serum-indepe ndent during S phase and mitosis. Post-translational modification of F ra-1 and Fra-2 causes a significant shift in their gel mobility which is eliminated by alkaline phosphatase treatment. Several kinases can p hosphorylate Fra-1 and Fra-2 in vitro, including cAMP-dependent kinase (PKA), protein kinase C (PKC), cyclin-dependent kinase 1-cdc2 (cdc2), and mitogen activated protein (MAP) kinase. From these, MAP kinase is the only one that causes a shift in gel mobility similar to that obse rved in vivo. One dimensional phosphopeptide maps of Fra-1 and Fra-2 p hosphorylated by MAP kinase in vitro are similar to those of in vivo l abeled Fra-1 and Fra-2, suggesting that MAP kinase may also phosphoryl ate Fra-1 and Fra-2 in vivo. We have also determined that phosphorylat ion of Fra-1 and Fra-2 by MAP kinase increases their DNA binding activ ity.