A new calcineurin inhibition domain in Cabin1.
Calcineurin (CN), a calcium-activated phosphatase, plays a critical role in various biological processes including T cell activation. Cabin1, a calcineurin binding protein 1, has been shown to bind directly to CN using its C-terminal region and inhibit CN activity. However, no increase in CN activity has been found in Cabin1DeltaC T cells, which produce a truncated Cabin1 lacking the C-terminal CN binding region. Here, we report that Cabin1 has additional CN binding domain in its 701-900 amino acid residues. Cabin1 (701-900) blocked both CN-mediated dephosphorylation and nuclear import of NFAT and thus inhibited IL-2 production in response to PMA/ionomycin stimulation. This fact may explain why Cabin1DeltaC mice previously showed no significant defect in CN-mediated signaling pathway.
Jang
Hyonchol
H
Department of Biochemistry and Molecular Biology, Cancer Research Institute, Interdisciplinary Program in Genetic Engineering, Seoul National University College of Medicine, 28 Yongon-dong, Chongro-gu, Seoul 110-799, Republic of Korea.
Cho
Eun-Jung
EJ
Youn
Hong-Duk
HD
D048868:Adaptor Proteins, Signal Transducing; D019703:Calcineurin / Q000737:chemistry* / Q000378:metabolism*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D011485:Protein Binding
D048868:Adaptor Proteins, Signal Transducing; C491861:CABIN1 protein, human; D004791:Enzyme Inhibitors; D019703:Calcineurin