Antibody News

Thrombomodulin, also known as BDCA-3, is a glycosylated transmembrane protein present on the surface of vascular endothelial cells. Thrombomodulin is a high-affinity receptor for thrombin, a key protein in the coagulation cascade. Formation of the thrombomodulin-thrombin complex blocks the thrombin dependent conversion of fibrinogen to fibrin and also catalyzes the activation of protein C. Active protein C is able to proteolytically inactivate enhancers of the coagulation cascade. Thrombomodulin’s dual ability to directly block thrombin function and to activate a negative regulator of coagulation makes it essential component of the anticoagulation system. Thrombomodulin is known for its role in anticoagulation but has recently been shown to have important functions in inflammation as well. The extracellular N-terminus of thrombomodulin consists of two domains; a lectin-like domain and an EGF-repeat domain. The EGF-repeat domain is responsible for thrombin binding...

Caspases are a family of cysteine-aspartic acid proteases that are responsible for the initiation and execution of apoptosis. Caspase-8 is a 55 kDa protein expressed as an inactive procaspase that resides in the cytosol. Activation of Caspase-8 requires cleavage into its large (17-21 kDa) and small (10-13 kDa) catalytic subunits. Caspase-8 has been shown to play a role in the induction of apoptosis by both death receptor mediated and non-receptor mediated mechanisms (1). Caspase-8 signals to effector Caspase-3 to execute apoptosis. Caspase-8 expression and activation is regulated on many levels. The prodomain of Procaspase-8 plays an important role in Caspase-8 activation. The prodomain interacts with FADD (Fas-Associated protein with Death Domain) to initiate apoptosis via the Fas/FasL pathway. The protein FLIP inhibits Caspase-8 activation by binding to FADD and preventing Procaspase-8 cleavage (1). Meanwhile, proteins of the inhibitors of apoptosis family (Survivin,...

Apoptosis is the tightly regulated process of programmed cell death. It plays an important role in normal physiologic development but has also been implicated in a number of diseases. Apoptosis is constantly downregulated by a family of anti-apoptotic proteins known as the inhibitors of apoptosis proteins (IAP). Every member of the IAP family contains one to three copies of a baculovirus IAP repeat (BIR domain). The BIR domain is a zinc-binding motif that allows these proteins to interact with and inhibit the pro-apoptotic caspases. One of the more recently characterized members of this family is Survivin, a 16.5 kDa protein, the smallest in the family. Survivin is unique in that it contains only one BIR domain and homodimerizes with itself before interacting with a caspase. Survivin plays a critical role in fetal development but is undetectable in healthy adult tissues. Ectopic expression of Survivin has been identified in a number of malignancies. Expression of...

Matrix metalloproteinases (MMPs) are responsible for the degradation of extracellular matrix proteins. MMPs are essential for tissue remodeling during normal processes such as embryonic development as well as pathological conditions such as arthritis and tumor metastasis. MMP3, a member of the stromelysin family, has broad specificity for proteins such as collagens, fibronectin, proteoglycans, and elastin making it an important player in extracellular matrix remodeling. These activities are especially important during tumorigenesis by enhancing epithelial to mesenchymal transition. MMPs are generally secreted as a proform and subsequently processed and cleaved into the active form. However under oxidative stress and during apoptotic signaling MMP3 can also be found in its active form inside of cells and may have important implications in neurodegenerative diseases like Alzheimer disease and Parkinson disease (1). A number of specific MMP inhibitors are currently in...

Calnexin is an abundant 90kDa chaperone protein that resides in the membrane of the endoplasmic reticulum. Calnexin and the related calreticulin protein function together to ensure the proper folding of glycoproteins. By binding to partially folded or misfolded proteins, Calnexin functions as an important quality control monitor ensuring proper folding of proteins destined for the plasma membrane or secretion. Calnexin contains a lectin site that recognizes substrate proteins through a transient and intermediate oligosaccharide containing a terminal glucose residue. Through this interaction calnexin binds to and participates in the folding of most if not all glycoproteins. Calnexin also contains binding sites for it cofactors ATP and Ca2+  and is able to recruit enzymes that catalyze disulfide bond formation and isomeriztion to aid in folding. Calnexin binding retains substrate proteins in the ER until they are fully mature and their...

Integrins are a family of transmembrane proteins involved in diverse processes including cell adhesion, signal transduction, cell migration, and differentiation. They exist as heterodimers consisting of noncovalently linked alpha and beta subunits. Integrin complexes span the plasma membrane and link the cytoskeleton with the extracellular matrix. In mammals there are 18 alpha and 8 beta subunits that can assemble into 24 distinct integrin heterodimers with alternative splicing adding even more diversity. In addition to binding the extracellular matrix, integrins also bind to endogenous ligands including soluble proteins and cell surface proteins. Integrin alpha v beta 3 (Integrin αvβ3), also known as the vitronectin receptor, has important roles in angiogenesis and tumor metastasis and binds to a wide range of extracellular matrix proteins containing the RGD-motif. Integrin alpha v beta 3 is highly expressed in cells of the bone, placenta, and invasive tumors where it...

The transforming growth factor-β (TGF-beta) family consists of a wide variety of signaling proteins with roles in development. TGF-beta signaling controls growth, differentiation, and immune responses and is often misregulated in cancer. TGF-beta 1 is the most widely expressed and abundant isoform of the TGF-beta family. TGF-beta proteins signal through two classes of receptors: type I (TβRI) and type II (TβRI). These receptor proteins are serine threonine kinases found at the cell surface. Binding of TGF-beta induces the formation of a heterocomplex with TβRI and TβRII and leads to the phosphorylation of TβRI by TβRII. The active phosphorylated form of TβRI recruits and phosphorylates downstream effector SMAD proteins, which can then translocate to the nucleus where they can regulate transcription. Non-canonical signaling by TGF-beta 1 can also be mediated through various pathways including MAPKs, small GTPases, and PI3Ks. TGF-beta proteins are synthesized as pro-...

Noxa is a BH3-only protein involved in regulating cell death decisions. Noxa is a primary p53-response gene and is upregulated in response to p53 overexpression or DNA damage. Noxa can also be induced by alternative mechanisms including through a hypoxia-response element found in its promoter. Noxa localizes to mitochondria where it binds to Mcl1, an anti-apoptotic Bcl2 family member. Binding of Mcl1 by Noxa not only neutralizes its pro-survival effects but can also lead to proteasomal degradation of Mcl1 to further enhance apoptosis. While Noxa is important for induction of cell death in some cellular contexts, overexpression of Noxa does not always lead to a strong apoptotic response. This suggests Noxa-induced cell death may depend on the levels of other Bcl2-like and BH3-only proteins within the cell. While the relevance of Noxa in tumor suppression is unclear insight into the regulation of...

Autophagy is important for the removal of damaged organelles or proteins as well as for the regulation of cellular homeostasis in response to stress. Proteins or organelles that are targeted for degradation are engulfed in a double-membrane structure called the autophagosome that eventually fuses with the lysosome to mediate cargo degradation. Atg5 plays an important regulatory role in the early steps of this process. During early autophagosome assembly Atg5 is conjugated to Atg12, an ubiquitin-like protein, and associates with Atg16. This complex of Atg5-Atg12/Atg16 forms a large multimeric complex and localizes to early autophagsome structure where it plays an essential role in the lipidation of Atg8. Atg8 is another ubiquitin-like protein that, upon lipidation, inserts into the autophagosome membrane to help recruit additional lipid components and autophagy machinery as well as cargo targeted for degradation. The...

Scavenger receptors play important roles in homeostasis and innate immunity by binding to endogenous and foreign molecules. Scavenger receptors on the plasma membrane of macrophages bind to ligand and allow their internalization and can also mediate pro- or anti-inflammatory signaling. The plasma membrane glycoprotein CD163 is a member of the scavenger receptor cysteine-rich (SRCR) protein family. CD163 contains nine SRCR domains and is expressed in macrophages and monocytes where it plays a role in innate immunity and regulation of inflammation in response to ligand binding. CD163 binds specifically to hemoglobin (Hb)-haptoglobin (Hp) complexes produced during hemolysis to allow their internalization and lysosomal degradation. Additionally, CD163 has been shown to bind other ligands including some bacterial or viral pathogens. Recognition of these ligands leads to internalization and breakdown as well as...

During autophagy ubiquitinated cargo or substrates are engulfed in a double-membrane autophagosome and transported to the lysosome for degradation. This process is important for maintaining cellular homeostasis and for degrading damaged organelles or misfolded protein aggregates. p62, also known as sequestosome 1 (SQSTM1), is an autophagy receptor that recognizes and recruits cargo to the autophagosome through its interaction with Atg8. Atg8, known as LC3 in mammals, is a ubiquitin-like protein that is conjugated to the lipid phosphatidylethanolamine which anchors it into the double-membrane phagopore structure. Atg8/LC3 is essential for binding to and recruiting the core autophagy machinery through an Atg8 interacting motif (AIM) or through the LC3-Interacting region (LIR). AIM/LIR containing autophagy receptors, including p62/SQSTM1, recognize ubiquitinated proteins and target them to the autophagosome for destruction. Autophagy is...