The WD motif-containing protein RACK-1 functions as a scaffold protein within the type I IFN receptor-signaling complex.
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.
Usacheva
Anna
A
Department of Pharmacology, University of Illinois, Chicago, IL 60612, USA.
Tian
Xinyong
X
Sandoval
Raudel
R
Salvi
Debra
D
Levy
David
D
Colamonici
Oscar R
OR
D020816:Amino Acid Motifs; D000818:Animals; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism* / Q000502:physiology; D053613:Janus Kinase 1; D008565:Membrane Proteins; D051379:Mice; D034521:Nuclear Matrix-Associated Proteins / Q000502:physiology*; D010766:Phosphorylation; D021122:Protein Subunits / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface / Q000378:metabolism / Q000502:physiology*; D018121:Receptors, Cytokine / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism / Q000502:physiology*; D020449:Repetitive Sequences, Amino Acid; D050794:STAT1 Transcription Factor; D015398:Signal Transduction / Q000276:immunology*; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000378:metabolism
D004268:DNA-Binding Proteins; D007370:Interferon Type I; D008565:Membrane Proteins; D034521:Nuclear Matrix-Associated Proteins; D021122:Protein Subunits; D011506:Proteins; D000075370:Receptors for Activated C Kinase; D011956:Receptors, Cell Surface; D018121:Receptors, Cytokine; D017471:Receptors, Interferon; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C494080:Stat1 protein, mouse; D015534:Trans-Activators; D053633:Receptor, Interferon alpha-beta; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1; D053634:TYK2 Kinase; C070139:TYK2 protein, human; C499356:Tyk2 protein, mouse