Lectins modulate the internalization of recombinant interferon-alpha A and the induction of 2',5'-oligo(A) synthetase.
After binding to specific cell surface receptors, interferon-alpha (IFN-alpha) along with its receptor is internalized by the cells. However, the physiological significance of the internalization of IFN is not known. We have found that the lectin concanavalin A (ConA), which does not inhibit the binding of 125I-rIFN-alpha A, inhibits both the internalization of 125I-rIFN-alpha A and the rIFN-alpha A-induced increase in the levels of 2',5'-oligo(A) synthetase mRNA and enzymatic activity in the B lymphoblastoid cell line Daudi. The reduced level of IFN-induced 2',5'-oligo(A) synthetase in ConA-treated cells was due neither to direct inhibition of the enzymatic activity nor to generalized inhibition of protein or RNA synthesis. The dose-response curves were similar for the effect of ConA to inhibit 125I-rIFN-alpha A internalization and 2',5'-oligo(A) synthetase induction. The correlation between the ConA-mediated inhibition of both 125I-rIFN-alpha A internalization and 2',5'-oligo(A) synthetase induction suggests that internalization of rIFN-alpha A plays a role in the responses to rIFN-alpha A. However, since ConA inhibits protein mobility in the plasma membrane, it is possible that ConA is also preventing aggregation of IFN receptors or interactions between IFN receptors and signal transducing proteins in the plasma membrane that may be necessary for responses to IFN.
Faltynek
C R
CR
Biological Carcinogenesis Development Program, National Cancer Institute-Frederick Cancer Research Facility, Maryland 21701.
Princler
G L
GL
Ruscetti
F W
FW
Birchenall-Sparks
M
M
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis*; D002460:Cell Line; D003208:Concanavalin A / Q000494:pharmacology*; D004790:Enzyme Induction; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D007700:Kinetics; D010835:Phytohemagglutinins / Q000494:pharmacology*; D011971:Receptors, Immunologic / Q000378:metabolism; D017471:Receptors, Interferon; D011994:Recombinant Proteins / Q000378:metabolism*
D007370:Interferon Type I; D010835:Phytohemagglutinins; D011971:Receptors, Immunologic; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D003208:Concanavalin A; D015088:2',5'-Oligoadenylate Synthetase