Cystatin C, Galectin-3, & Rae-1 beta

Cystatin C

Cystatin C is a member of the cystatin superfamily. Ubiquitous in human tissues and body fluids, cystatin C is involved in processes such as tumor invasion and metastasis, inflammation, and several neurological diseases. It also inhibits many cysteine proteases, such as papain and cathepsins B, H, K, L, and S. A point mutation in the gene coding for the 120 amino acid mature cystatin C causes a hereditary form of amyloid angiopathy in which the protein variant (Leu68 to Gln) is deposited in the cerebral arteries, leading to fatal cerebral hemorrhage. Additional clinical applications may also exist. For example, it is a useful marker for monitoring glomerular filtration rate.


The galectins constitute a large family of carbohydrate-binding proteins with specificity for N-acetyl-lactosamine-containing glycoproteins. At least 14 mammalian galectins, which share structural similarities in their carbohydrate recognition domains (CRD), have been identified to date. Galectin-3, also known as Mac-2, L29, CBP35, and eBP, is expressed in tumor cells, macrophages, activated T cells, osteoclasts, epithelial cells, and fibroblasts. It binds various matrix glycoproteins, promotes cell growth and proliferation, acts intracellularly to prevent apoptosis, and depending on the cell type, exhibits pro- or anti-adhesive properties. Galectin-3 also induces pro-inflammatory activities, inhibits Th2 type cytokine production, chemoattracts monocytes and macrophages, and activates and degranulates basophils and mast cells. Elevated circulating levels of Galectin-3 correlate with the malignant potential of several types of cancer, suggesting that Galectin-3 is also involved in tumor growth and metastasis. Human and mouse Galectin-3 share approximately 80% amino acid sequence similarity.

Rae-1 beta/Fc Chimera

Rae-1 beta is a member of a cell surface protein family that function as ligands for mouse NKG2D. Other family members include Rae-1 alpha, gamma, delta, and epsilon. Rae-1 proteins, anchored to the membrane via a GPI-linkage, are distantly related to MHC class I proteins. They possess only the alpha 1 and alpha 2 Ig-like domains, however, and are incapable of binding peptide or interacting with beta2-microglobulin. The genes encoding these proteins are not found within the major histocompatibility complex on mouse chromosome 17 but rather map to mouse chromosome 10.

Rae-1 expression is developmentally controlled with transcripts observed in the brain/head region of day 10 - 14 embryos but not day 18 embryos. Rae-1 transcripts have also been detected in several transformed cell lines but are absent from most normal adult tissues. All Rae-1 family members bind to mouse NKG2D, an activating receptor expressed on NK cells and some T cell subsets, thus resulting in the activation of cytolytic activity and/or cytokine production by these effector cells. Ectopic expression of Rae-1 on mouse tumor cell lines results in in vivo rejection of the tumors.