PKC iota, Active

PKC ι is a member of the protein kinase C family of serine-threonine kinases. The amino acid sequence of PKC ι showed greatest homology to PKC zeta, with 72% identity overall rising to 84% in the catalytic domain. In contrast, the homology of PKC ι to the other isoforms is less pronounced, with < 53% identity even in the highly conserved catalytic region. PKC ι transcript is present predominantly in lung and brain, but also expressed at lower levels in many tissues including pancreatic islets. PKC ι is stimulated by tumor necrosis factor α (TNF-α) and is required for the activation of NF-kB by this cytokine. Cell transfections with a PKC ι dominant negative mutant abolished TNF-α-induced NFkB-dependent transcription. PKC ι can modify vulnerability of neural cells to apoptosis induced by amyloid β-peptide (ABP), a cytotoxic peptide linked to neuronal degeneration in Alzheimer's disease. Associated with the increased resistance to apoptosis are improved mitochondrial function and reduced activity of caspases. In addition, ABP-induced increases in levels of oxidative stress and intracellular calcium levels were attenuated in cells overexpressing PKC ι.