The PH domain containing protein CKIP-1 binds to IFP35 and Nmi and is involved in cytokine signaling.

The pleckstrin homology domain-containing protein CKIP-1 is implicated in regulation of cell differentiation, apoptosis, cytoskeleton as well as recruitment of CK2 and ATM kinases to plasma membrane. Protein-protein interactions of CKIP-1 were required for these functions. Here we identify the IFN-induced protein IFP35 and its homologue Nmi as two novel ...
CKIP-1 interacting partners. The NID domains of IFP35 and Nmi are required for the interactions. Similar to IFP35 and Nmi, CKIP-1 can be up-regulated dramatically by IFN-gamma and IL-2 and form homodimer and homotrimer in vivo. Nmi stabilizes IFP35, whereas CKIP-1 destabilizes IFP35 via inhibiting IFP35-Nmi interaction. The ratio of Nmi to CKIP-1 determines the stability of IFP35 and control cytokine signaling in a novel mechanism. Importantly, similar to Nmi and contrast to IFP35, CKIP-1 inhibits tumor cell growth and Akt-mediated cell survival. Thus, our results provide a novel role of CKIP-1 in cytokine signaling response and the biochemical mechanism, by which two previously identified modulators IFP35 and Nmi are involved via interactions.
Mesh Terms:
Animals, Blotting, Northern, Carrier Proteins, Cell Line, Cell Line, Tumor, DNA, Complementary, Dimerization, Gene Library, Hela Cells, Humans, Interferon-gamma, Interleukin-2, Intracellular Signaling Peptides and Proteins, Leukocytes, Mononuclear, Mice, NIH 3T3 Cells, Protein Binding, Protein Structure, Tertiary, Signal Transduction, Two-Hybrid System Techniques, Up-Regulation
Cell. Signal.
Date: May. 01, 2007
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