Regulated proteolysis of the IFNaR2 subunit of the interferon-alpha receptor.

The type I interferons (IFNs) bind surface receptors, induce JAK kinases and activate STAT transcription factors to stimulate the transcription of genes downstream of IFN-stimulated response elements (ISREs). In this study, we demonstrate that IFNaR2, a subunit of the type I IFN receptor, is proteolytically cleaved in a regulated manner. Immunoblotting shows that multi-step cleavage occurs in response to phorbol ester (PMA) and IFN-alpha, generating both a transmembrane 'stub' and the intracellular domain (ICD), similar to Notch proteolysis.