ABSTRACT
I. INTERFERONS ARE CYTOKINES Interferons (IFNs) were the first cytokines purified and cloned (1). They interact with multisubunit receptors on the cell surface. Cytokines are proteins which carry directives from cell to cell, bind to a specific receptor, and activate a direct signal transduction pathway. The signal transduction pathways activated by IFNs directly activate a recently identified class of enzymes, known as Janus kinases (JAKs) (like the Roman god Janus, they have two faces; i.e., two active sites). Activated JAKs, apparently attached to the intracellular domain of the cytokine receptor, phosphorylate intracellular proteins called signal transducers and activators of transcription (STAT). Phosphorylated STATs form a protein complex that moves to the nucleus and directly binds to the IFN-stimulated response element, a DNA element common to the promoters that control transcription of IFN-inducible genes. Although other cytokines bind different cell receptors, IFNs share JAK or STAT proteins with some cytokines (2). This may explain why IFNs modulate, as well as share, biological effects with other cytokines.
