Activation of PKC is one of the earliest events in a cascade leading to a variety of cellular responses such as secretion, gene expression, proliferation and muscle contraction. Protein kinase D (PKD), also called PKCmicro, is a serine/threonine kinase whose activation is dependent on the phosphorylation of two activation loop sites, Ser744 and Ser748, via a PKC-dependent signaling pathway. In addition to the two activation loop sites, the carboxy-terminal Ser916 has been identified as an autophosphorylation site for PKD/PKCmicro. Phosphorylation at Ser916 correlates with PKD/PKCmicro catalytic activity.