Multichain structure of the IFN-alpha receptor on hematopoietic cells.
The structure of IFN-alpha receptor was studied by 1) developing antibodies against the receptor, and 2) screening a number of cell lines by affinity cross-linking to identify cells that express different IFN-alpha 2 receptor structures. We report that two different patterns of IFN-alpha 2 receptor are observed in human cells of hematopoietic origin. The predominant form of the IFN-alpha receptor is a multichain structure in which IFN-alpha 2 forms complexes of 110 and 130 kDa (alpha-subunit). A high Mr complex of 210 kDa results from the association of alpha-subunit and other receptor components. In contrast, another form of the receptor has been identified in the IFN-alpha-resistant U-937 cell line and in some cases of acute leukemia. This form of the IFN-alpha receptor is characterized by the presence of the alpha- subunit, and the absence of the 110- and 210-kDa bands. Also a novel 180-kDa complex and a more prominent 75-kDa band are observed. Functional studies performed in U-937 cells showed that this cell line is not only partially resistant to the antiproliferative and antiviral effects of IFN-alpha, but also fails to down-regulate the alpha-subunit of the IFN-alpha receptor upon IFN-alpha binding.
Colamonici
O R
OR
Department of Medicine, University of Chicago, IL 60637.
Pfeffer
L M
LM
D'Alessandro
F
F
Platanias
L C
LC
Gregory
S A
SA
Rosolen
A
A
Nordan
R
R
Cruciani
R A
RA
Diaz
M O
MO
D002460:Cell Line; D015536:Down-Regulation; D006031:Glycosylation; D006413:Hematopoietic System / Q000737:chemistry*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism* / Q000494:pharmacology; D007938:Leukemia / Q000378:metabolism; D011971:Receptors, Immunologic / Q000032:analysis* / Q000737:chemistry; D017471:Receptors, Interferon
D016898:Interferon-alpha; D011971:Receptors, Immunologic; D017471:Receptors, Interferon