Protein kinase C isoforms can be activated by the second messenger inputs calcium (Ca2+) and DAG generated by the activity of PLC. Intracellular calcium activates PKCα, β and γ via their C2 domains, while DAG and TPA activate PKCα, β, γ, δ, ε, η and θ via C1 domains. Src family kinases can also tyrosine phosphorylate and alter the expression of PKCδ. The outputs of PKC signaling are isoform dependent as indicated: PKCα (differentiation-associated growth arrest and cytokine-mediated inflammation), PKCβ (melanogenesis), PKCδ (squamous differentiation, growth arrest and apoptosis), PKCη (squamous differentiation and growth arrest), PKCε (hyperplasia).