Protein Kinase C and Apoptosis

The protein kinase C (PKC) family consists of ten structurally related serine/threonine protein kinases. PKC isoforms are critical regulators of cell proliferation and survival and their expression or activity is altered in some human diseases, particularly cancer. The development and utilization of PKC isoform specific tools, including dominant inhibitory kinases, mouse models in which specific PKC isoforms have been disrupted, and PKC isoform specific antisense/siRNA, has allowed studies to define isoform-specific functions of PKC in the apoptotic pathway. From these approaches a pattern is emerging in which the conventional isoforms, particularly PKCα and PKCβ, and the atypical PKCs, PKCι/λ and PKCζ, appear to be anti-apoptotic/pro-survival. The novel isoform, PKCδ, is primarily pro-apoptotic, whereas PKCε in most studies appears to suppress apoptosis. The identification of both proand anti-apoptotic isoforms suggests that PKC isoforms may function as molecular sensors, promoting cell survival under favorable conditions, and executing the death of abnormal or damaged cells when needed.This chapter discusses what is currently known about the contribution of specific isoforms to apoptosis, and how signal transduction by PKC integrates with other molecular regulators to promote or inhibit apoptosis.