Antibodies to S100 Family

Introduction:

One of the largest subfamilies of EF-hand Ca2+-binding proteins is constituted by the S100 proteins. They comprise different human members which display a diverse pattern of cell- and tissue-specific distribution consistent with their pleiotropic intra- and extracellular functions. These functions are brought about through interaction with diverse target proteins, probably sometimes in a concerted manner with the ubiquitously expressed calmodulin.

A wide range of diseases, including cardiomyopathies, neurological diseases, chronic inflammation, and cancer were recently linked to deregulation of S100 gene expression. Hence, S100 proteins are currently considered for their potential use in clinical diagnostics as well as for therapeutic interventions.

Protein Structure and Biochemical Properties

S100 proteins are characterized by two distinct EF-hand calcium-binding motifs with different affinities. Usually, the carboxy-terminal EF-hand is referred to as the canonical Ca2+-binding loop with a rather high affinity, whereas the amino-terminal loop is S100 specific and displays lower Ca2+-binding affinity. These EF-hands are flanked by hydrophobic regions, responsible for interaction with target proteins, and separated by a central hinge region. Generally, S100 proteins can form homo- or heterodimers and bind 4 Ca2+ per dimer. Several S100 proteins also bind Zn2+, however to a different site. Zn2+-binding is able to modify the Ca2+ affinity in a few cases. Furthermore, S100B and S100A5 also bind Cu2+. Therefore, there is considerable variation in the biochemical and metal-binding properties of S100 proteins the physiological consequences of which remain to be investigated.

Biological Functions

S100 proteins are involved in a large number of cellular activites such as signal transduction, cell differentiation, regulation of cell motility, transcription and cell cycle progression which are brought about through modulation of target proteins in a Ca2+-, and possibly also in a Zn2+- and Cu2+-dependent manner. In general, one can distinguish intracellular functions of S100 proteins such as regulation of protein phosphorylation, cytoskeletal assembly, transcription or enzyme activities from extracellular functions. These extracellular functions include chemotactic activity (S100A8 and S100A9) as well as neurotrophic acitivities (S100B). However, the mechanisms of secretion as well as the nature of high affinity surface receptors are largely unknown. One good candidate for such a receptor might be the receptor for advanced glycosylation end-products (RAGE) which was recently shown to bind S100B and S100A12.

Antibody Tools for the Detection of S100 Proteins

During the last years interest in antibodies to proteins of the S100 family increased dramatically. Therefore, more and more antibodies were added to our product list and the antibody panel grew to one of the largest collections of antibodies to S100 Proteins. Nearly all antibodies can be used for Western blotting, many of them are suitable for immunohistochemistry procedures and/or ELISA techniques.

Fig.1: Western blot of S100-alpha from human muscle extract using antibody SP5355P.

Fig.2: Formalin-fixed, paraffin-embedded human melanoma stained with anti-S100A4 ( antibody AP00589) using AEC chromogen. Note cytoplasmic staining of tumor cells.

Fig.3: Formalin-fixed, paraffin-embedded human tonsil stained with anti-S100A6 (antibody AP00590) using peroxidase-conjugate and AEC chromogen. Note cytoplasmic staining of cells in germinal center.

Fig.4: Immunohistochemical analysis of S100A7 (Psoriasin) expression in ductal carcinoma in situ. Shown are successive sections of H&E staining, a control monoclonal antibody, and antibody SM7033 (left to right).

Fig.5: Western blot analysis of Psoriasin in confluent MCF10A cells using antibody SM7033 at 1 µg/ml.

Fig.6: S100A8/9 staining in frozen sections human tonsil using antibody BM4025.

Available Antibody Panel to S100 Family

S100A1, S100A2, S100A3, S100A4, S100A5 - antibody, S100A6 (Calcyclin) antibody, S100A7 (Psoriasin, HID-5) antibody, S100A8 (MRP8, Calgranulin A) antibody, S100A8/9 (MRP8/14, Calgranulin A/B, Calprotectin) antibody, S100A9 (MRP14, Calgranulin B) antibody, S100A10 (Calpactin, Annexin A2 light chain p11) antibody, S100A11, S100A13, S100A14 - antibody, S100A/B antibody, S100B antibody, S100P antibody

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