A region of the beta subunit of the interferon alpha receptor different from box 1 interacts with Jak1 and is sufficient to activate the Jak-Stat pathway and induce an antiviral state.
Coexpression of the alpha and betaL subunits of the human interferon alpha (IFNalpha) receptor is required for the induction of an antiviral state by human IFNalpha. To explore the role of the different domains of the betaL subunit in IFNalpha signaling, we coexpressed wild-type alpha subunit and truncated forms of the betaL chain in L-929 cells. Our results demonstrated that the first 82 amino acids (AAs) (AAs 265-346) of the cytoplasmic domain of the betaL chain are sufficient to activate the Jak-Stat pathway and trigger an antiviral state after IFNalpha2 binding to the receptor. This region of the betaL chain, required for Jak1 binding and activation, contains the Box 1 motif that is important for the interaction of some cytokine receptors with Jak kinases. However, using glutathione S-transferase fusion proteins containing amino- and carboxyl-terminal deletions of the betaL cytoplasmic domain, we demonstrate that the main Jak1-binding region (corresponding to AAs 300-346 on the beta subunit) is distinct from the Box 1 domain (AAs 287-295).
Domanski
P
P
Department of Pathology, University of Tennessee, Memphis, Tennessee 38163, USA.
Fish
E
E
Nadeau
O W
OW
Witte
M
M
Platanias
L C
LC
Yan
H
H
Krolewski
J
J
Pitha
P
P
Colamonici
O R
OR
D000818:Animals; D002460:Cell Line; D003593:Cytoplasm / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D053613:Janus Kinase 1; D051379:Mice; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D016898:Interferon-alpha; D017471:Receptors, Interferon; D011993:Recombinant Fusion Proteins; D053633:Receptor, Interferon alpha-beta; D005982:Glutathione Transferase; D011505:Protein-Tyrosine Kinases; C507904:JAK1 protein, human; C507905:Jak1 protein, mouse; D053613:Janus Kinase 1