Role of regulatory domain mutants of PKC isoforms in c-fos induction

Protein kinase C (PKC) is a multi-gene family of serine-threonine protein kinases, composed of at least 10 kinases.1 Classical and novel PKC isoforms are activated by diacyl-glycerol (DAG) and induce survival pathways in various cells. A tandem repeat of cysteine-rich motif referred to as the C1a and C1b domain in the regulatory domain is thought to be responsible for this activation. Atypical PKC isoforms, which lack of the C1b domain, cannot be activated by DAG.1 A DAG analog 12-O-tetradecanoylphorbol-13-acetate (TPA) is known to activate PKC, resulting in diverse cellular func-tions such as cell proliferation, differentiation and tumori-genesis. PKC can activate extracellular signal-regulated kinase (ERK) through mitogen-activated protein (MAP) kinases. Activated ERK translocates to the nucleus and regulates the activity of many transcription factors.2 Ternar