Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting
Background: The annexin superfamily consists of 13 calcium or calcium and phospholipid binding proteins with high biological and structural homology (1). Annexin-1 (ANXA1) is the first characterized member of the annexin family of proteins and is able to bind to cellular membranes in a calcium-dependent manner, promoting membrane fusion and endocytosis (2-4). Annexin A1 has anti-inflammatory properties and inhibits phospholipase A2 activity (5,6). Annexin A1 can accumulate on internalized vesicles after EGF-stimulated endocytosis and may be required for a late stage in inward vesiculation (7). Phosphorylation by PKC, EGFR, and Chak1 results in inhibition of annexin A1 function (8-10). Annexin A1 has also been identified as one of the 'eat-me' signals on apoptotic cells that are to be recognized and ingested by phagocytes (11). Annexin A1, as an endogenous anti-inflammatory mediator, has roles in many diverse cellular functions, such as membrane aggregation, inflammation, phagocytosis, proliferation, apoptosis, and tumorigenesis and cancer development (12-14).
|Human, Mouse, Rat|
Application Methods: Immunoprecipitation, Western Blotting
Background: The adhesive glycoprotein thrombospondin-1 (THBS1, TSP1) localizes to the extracellular matrix (ECM) and mediates interactions between cells and the ECM and among cells. Thrombospondin-1 is a multi-domain, glycosylated protein that interacts with a wide variety of extracellular targets, including matrix metalloproteinases (MMPs), collagens, cell receptors, growth factors, and cytokines (1). The protein structure of THBS1 includes an amino-terminal laminin G-like domain, a von Willebrand factor-binding domain, and multiple thrombospondin (TSP) repeated sequences designated as type I, type II, or type III repeats. Each thrombospondin domain interacts with a distinct type of cell surface ligands or protein targets. The amino-terminal domain interacts with aggrecan, heparin, and integrin proteins. Type I TSP repeats interact with MMPs and CD36, while carboxy-terminal repeats bind the thrombospondin receptor CD47 (1). Through these interactions, THBS1 exerts diverse effects on different signaling pathways, such as VEGF receptor/NO signaling, TGFβ signaling, and the NF-κB pathway (2-5). Thrombospondin-1 is an important regulator of many biological processes, including cell adhesion/migration, apoptosis, angiogenesis, inflammation, vascular function, and cancer development (2-5). The activity of thrombospondin-1 is mainly regulated by extracellular proteases. The metalloproteinase ADAMTS1 cleaves thrombospondin, resulting in the release of peptides with anti-angiogenic properties. Elastase and plasmin proteases degrade the THBS1 protein and down regulate its activity (6). As THBS1 is an important protein inhibitor of angiogenesis, the development of thrombospondin-based compounds and their use in therapeutic studies may provide a beneficial approach to the treatment of cancer (7,8).
|Human, Monkey, Mouse, Rat|
Application Methods: Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Western Blotting
Background: Transglutaminase 2 (TGM2) is a calcium-dependent enzyme that cross-links both cytosolic and extracellular matrix proteins by catalyzing the formation of bonds between lysine and glutamine residues (1). This bifunctional enzyme also has intrinsic GTPase activity, and it has been suggested that regulation of the transamidase activity might be regulated through a G-protein coupled receptor-signaling pathway (2). In cross-linking peptides, TGM2 helps to regulate cytoskeletal structure, cell migration, apoptosis and cell-matrix adhesion. In addition, the enzyme plays an important role in wound healing and the immune response (3). TGM2 has exhibited kinase activity in vitro, with insulin-like growth factor-binding protein-3 (IGFBP-3) as one possible substrate (4). This widely expressed protein is localized to the cytosol and nucleus, but has also been isolated from the cell surface and extracellular matrix (reviewed in 5). Because of its interaction with a number of different substrates, and its role in the response to injury, TGM2 has been associated with the pathology of a number of human disorders. It has long been recognized as the major autoantigen in celiac disease (6); altered TGM2 expression or activity may be associated with Alzheimer disease, Huntington disease, arteriosclerosis, diabetes, and numerous forms of cancer (reviewed in 7).