Protein kinase C theta: evolution, regulation, and function

Abstract Protein kinase C (PKC) is a family of serine/threonine kinases whose nine members play central roles in signal transduction, regulating key cellular processes such as proliferation, migration, differentiation, and apoptosis. PKC theta (θ) is a member of the diacylglycerol-regulated novel-d PKC subfamily and differentiates itself from other family members in its selective expression in hematopoietic cells, where it is essential for T cell activation, differentiation, and survival. Given its pivotal role in immune signaling, dysregulated PKCθ has been implicated in inflammatory and autoimmune diseases, as well as cancer. However, unlike the extensively studied Ca2+-regulated conventional PKC isozymes, the mechanisms of PKCθ and its roles in both health and disease remain relatively unexplored. In this review, we examine the evolution of PKCθ, its domain structure and lifecycle, its role in immune signaling, and its relevance in disease.