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Dimerization and DNA binding alter phosphorylation of Fos and Jun
C Abate1, S J Baker, S P Lees-Miller
1Roche Institute of Molecular Biology, Roche Research Center, Nutley, NJ 07110.
Summary
Fos and Jun protein phosphorylation by kinases is altered by dimerization and DNA binding. Different kinases recognize distinct Fos-Jun states, suggesting independent regulation of gene transcription via activator protein 1 (AP-1) signaling.
Area of Science:
- Molecular Biology
- Cell Signaling
- Gene Regulation
Background:
- Fos and Jun proteins form dimers that bind activator protein 1 (AP-1) DNA sites, regulating gene expression.
- Their activity is modulated by extracellular stimuli and involves complex nuclear signal transduction.
- Regulation mechanisms include dimerization, interactions with other factors, and post-translational modifications like phosphorylation.
Purpose of the Study:
- To investigate how dimerization and DNA binding affect Fos and Jun phosphorylation by various protein kinases.
- To determine if different protein kinases can distinguish between various states of Fos and Jun proteins.
Main Methods:
- Studied phosphorylation of Fos and Jun monomers, homodimers, and heterodimers.
- Assessed the impact of DNA binding to AP-1 sites on protein phosphorylation.
- Utilized multiple protein kinases including casein kinase II, cdc2 kinase, protein kinase C, cAMP-dependent protein kinase, and DNA-dependent protein kinase.
Main Results:
- Jun homodimers are efficiently phosphorylated by casein kinase II, unlike Fos-Jun heterodimers.
- DNA binding reduces Jun phosphorylation by casein kinase II, cdc2, and protein kinase C.
- Fos phosphorylation by cAMP-dependent protein kinase and cdc2 is largely unaffected by dimerization or DNA binding.
- DNA-dependent protein kinase phosphorylation of Fos and Jun is significantly enhanced upon binding to the AP-1 site.
Conclusions:
- Protein kinases can differentiate between Fos and Jun proteins in monomeric, homodimeric, and heterodimeric forms.
- Kinases also distinguish between DNA-bound and non-DNA-bound Fos and Jun proteins.
- These findings suggest that distinct phosphorylation events allow for independent regulation of Fos and Jun activity and AP-1-mediated gene transcription.