The WD Motif-Containing Protein RACK-1 Functions as a Scaffold Protein Within the Type I IFN Receptor-Signaling Complex

• Published in: The Journal of immunology (1950) Vol. 171; no. 6; pp. 2989 - 2994
• Main Authors: Usacheva, Anna, Tian, Xinyong, Sandoval, Raudel, Salvi, Debra, Levy, David, Colamonici, Oscar R
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 15.09.2003
• Subjects: Amino Acid Motifs; Animals; Cell Line, Tumor; DNA-Binding Proteins - metabolism; Humans; Interferon Type I - metabolism; Interferon Type I - physiology; Janus Kinase 1; Membrane Proteins; Mice; Nuclear Matrix-Associated Proteins - physiology; Phosphorylation; Protein Subunits - metabolism; Protein-Tyrosine Kinases - metabolism; Proteins - metabolism; Receptor, Interferon alpha-beta; Receptors for Activated C Kinase; Receptors, Cell Surface - metabolism; Receptors, Cell Surface - physiology; Receptors, Cytokine - metabolism; Receptors, Interferon - metabolism; Receptors, Interferon - physiology; Repetitive Sequences, Amino Acid; Signal Transduction - immunology; STAT1 Transcription Factor; Trans-Activators - metabolism; TYK2 Kinase
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.171.6.2989

The WD repeat-containing protein receptor for activated protein kinase C (RACK)-1 has been linked to a variety of signaling systems including protein kinase C, growth factors, and IFNs. In the IFN system, RACK-1 functions as an adaptor recruiting the transcription factor STAT1 to the receptor complex. However, RACK-1 should play a broader role in type I IFN signaling because mutation of the RACK-1 binding site in the IFN-alpha receptor 2/beta subunit of the type I IFN receptor abrogates not only STAT1, but also STAT2, activation. In this study, we demonstrate that RACK-1 serves as a scaffold protein for a multiprotein complex that includes the IFN-alpha receptor 2/beta-chain of the receptor, STAT1, Janus kinase 1, and tyrosine kinase 2. In vitro data further suggest that within this complex tyrosine kinase 2 is the tyrosine kinase responsible for the phosphorylation of STAT1. Finally, we provide evidence that RACK-1 may also serve as a scaffold protein in other cytokine systems such as IL-2, IL-4, and erythropoietin.