Carbohydrate recognition site of interleukin-2 in relation to cell proliferation.
Interleukin-2 (IL-2) is a cytokine with important roles in the immune system. IL-2 initially binds a high mannose-type glycan and a specific peptide sequence of the IL-2 receptor alpha-subunit and sequentially forms a high affinity complex of IL-2.IL-2 receptor alpha-, beta-, and gamma-subunits. This formation induces cellular signaling and cell proliferation (Fukushima, K., and Yamashita, K. (2001) J. Biol. Chem. 276, 7351-7356). To determine the carbohydrate-binding site of IL-2, we prepared wild-type and point-mutated (35)S-IL-2 by an in vitro transcription and translation method. We found that wild-type (35)S-IL-2 tends to form a dimer spontaneously, and the dimeric form has both carbohydrate recognition activity and cell proliferation activity. Moreover, substitution of Asn-26 in IL-2 with Gln or Asp conserved the dimeric form and affected the carbohydrate recognition activities in correspondence with the cell proliferation activities, suggesting that Asn-26 in IL-2 is involved in the carbohydrate recognition site. These results suggest that the carbohydrate recognition of IL-2 dimer triggers formation of high affinity complex (IL-2.IL-2Ralpha, -beta, -gamma)(2), and the hetero-octamer stimulates IL-2-dependent T-cell proliferation by intensifying cellular signaling.
Fukushima
K
K
Department of Biochemistry, Sasaki Institute, 2-2 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan.
Hara-Kuge
S
S
Ideo
H
H
Yamashita
K
K
D000818:Animals; D001665:Binding Sites; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D019281:Dimerization; D007376:Interleukin-2 / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D017354:Point Mutation; D011134:Polysaccharides / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
D007376:Interleukin-2; D011134:Polysaccharides; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins