Phosphorylation of c-jun mediated by MAP kinases

Area of Science:

• Molecular Biology
• Cell Signaling
• Oncogenesis

Background:

• Proto-oncogene c-jun is a transcription factor regulating nuclear events.
• c-jun activity is modulated by phosphorylation, particularly dephosphorylation at the carboxy terminus.
• Extracellular stimuli, including phorbol esters, influence c-jun activity.

Purpose of the Study:

• To identify specific phosphorylation sites on c-jun regulated by mitogens.
• To investigate the role of mitogen-activated protein (MAP) kinases in c-jun phosphorylation.
• To determine how MAP kinase-mediated phosphorylation affects c-jun's transcriptional activity.

Main Methods:

• Phosphorylation site mapping of c-jun.
• In vitro kinase assays using purified MAP kinases (pp54, pp42/44).
• Analysis of c-jun transactivation activity following phosphorylation.

Main Results:

• Two serine residues in the c-jun amino-terminal A1 domain were identified as targets for phosphorylation.
• Mitogens, phorbol esters, and activated ras induce phosphorylation at these sites.
• MAP kinases pp54 and pp42/44 specifically phosphorylate these serine residues, leading to increased c-jun transactivation.

Conclusions:

• MAP kinase-mediated phosphorylation of specific serine residues in the A1 domain positively regulates c-jun activity.
• This mechanism provides insight into how mitogens, growth factors, and oncogenes commonly stimulate c-jun.
• The findings highlight a key regulatory pathway in cellular responses to growth signals.