Human leukocyte interferon (IFN-alpha) binds to discrete cell surface receptors on target cells, and thereby alters gene expression. Transmembrane signaling by IFN-alpha involves the production of DAG without an increased intracellular free calcium concentration, and the subsequent activation of calcium-independent isoforms of PKC (beta and epsilon). Selective PKC inhibitors (H-7 and staurosporine) can block the ability of IFN-alpha to activate the transcription of a distinct set of genes, called the IFN-stimulated genes (ISG), and to protect cells against viral infection. IFN-alpha also induces the rapid changes in protein phosphorylation, which may include latent transcription factors for ISGs.