Bootcov, MR, Bauskin, AR, Valenzuela, SM, Moore, AG, Bansal, M, He, XY, Zhang, HP, Donnellan, M, Mahler, S, Pryor, K, Walsh, BJ, Nicholson, RC, Fairlie, WD, Por, SB, Robbins, JM & Breit, SN 1997, 'MIC-1, a novel macrophage inhibitory cytokine, is a divergent member of the TGF-β superfamily', Proceedings of the National Academy of Sciences, vol. 94, no. 21, pp. 11514-11519.
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Macrophages play a key role in both normal and pathological processes involving immune and inflammatory responses, to a large extent through their capacity to secrete a wide range of biologically active molecules. To identify some of these as yet not characterized molecules, we have used a subtraction cloning approach designed to identify genes expressed in association with macrophage activation. One of these genes, designated macrophage inhibitory cytokine 1 (MIC-1), encodes a protein that bears the structural characteristics of a transforming growth factor β (TGF-β) superfamily cytokine. Although it belongs to this superfamily, it has no strong homology to existing families, indicating that it is a divergent member that may represent the first of a new family within this grouping. Expression of MIC-1 mRNA in monocytoid cells is up-regulated by a variety of stimuli associated with activation, including interleukin 1β, tumor necrosis factor α (TNF-α), interleukin 2, and macrophage colony-stimulating factor but not interferon γ, or lipopolysaccharide (LPS). Its expression is also increased by TGF-β. Expression of MIC-1 in CHO cells results in the proteolytic cleavage of the propeptide and secretion of a cysteine-rich dimeric protein ofMr25 kDa. Purified recombinant MIC-1 is able to inhibit lipopolysaccharide -induced macrophage TNF-α production, suggesting that MIC-1 acts in macrophages as an autocrine regulatory molecule. Its production in response to secreted proinflammatory cytokines and TGF-β may serve to limit the later phases of macrophage activation.
Valenzuela, SM, Martin, DK, Por, SB, Robbins, JM, Warton, K, Bootcov, MR, Schofield, PR, Campbell, TJ & Breit, SN 1997, 'Molecular Cloning and Expression of a Chloride Ion Channel of Cell Nuclei', Journal of Biological Chemistry, vol. 272, no. 19, pp. 12575-12582.
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Ion channels are known to be present on the plasma membrane of virtually all cells and have been found on the membranes of various intracellular organelles. However, until recently they were believed not to occur at the nuclear membrane. In this study we describe the molecular cloning and characterization of a nuclear ion channel protein, designated nuclear chloride channel-27 (NCC27), from the human myelomonocytic cell line, U937. NCC27 is a novel chloride ion channel protein that was found to localize principally to the cell nucleus, Its only known homologue is a bovine chloride ion channel protein (p64) believed to localize to internal organelles. NCC27 therefore represents the first human member of a new class of organellar chloride ion channel proteins.
