Perforin is a calcium-dependent pore forming cytolytic protein. Perforin is partially homologous to the terminal components of the membrane attack complex of complement and produces pores of up to 20nm in diameter on target membranes. Killer lymphocytes release perforin and granzymes from cytotoxic granules into the immunological synapse to destroy target cells as a critical mechanism in the defense against viruses and cancer (1).
-Western-Blot-NBP1-97512-img0001.jpg "Western Blot: Perforin Antibody")
Increased perforin...
Over the past two decades, it has become clear that tyrosine phosphorylation plays a pivotal role in a variety of important signaling pathways in multicellular organisms. In the typical vertebrate cell, phosphotyrosine represents only a tiny fraction of total protein phosphorylation. Yet it is sufficient enough to induce malignant transformation (1), as unregulated phosphotyrosine signaling causes a breakdown in the normal regulation of cellular processes leading to several human diseases (2).
-Western%20Blot-NB600-907-img0001.jpg "Western Blot: Phosphotyrosine Antibody")
The oncogenic signaling pathways driving cell...
Synaptophysin (a presynaptic vesicle protein) is an integral membrane glycoprotein originally isolated from presynaptic vesicles of bovine neurons. Synaptophysin is found in all nerve terminals and synaptophysin measurements have been used to quantify the number of terminals present during neuroanatomical remodeling and neural development (1). Accumulation of beta Amyloid and loss of synapses are hallmarks of Alzheimer's disease.
Phosphoserine is an ester of serine and phosphoric acid which results from posttranslational modifications. Phosphorylation is a key post-translational modification necessary for normal cellular signaling. Phosphorylated proteins mediate cell division, cellular differentiation, signal transduction and other key cellular signaling processes. Phosphorylation of serine residues on proteins is one of the keys to a cascade of reactions that are of great interest to many researchers. Phosphorylated serine residues have been detected by...
Myosin is a super family of actin based molecular motors that hydrolyze ATP and generate physical force to move specific molecules inside the cell. This super family, divided into at least twenty four classes based on head domain sequence similarity and domain organization. The processivity of myosins along an actin filament and transport of intracellular ‘cargo’ are achieved by generating physical force from chemical energy of ATP followed by appropriate conformational changes (1).
Myosin has raised an interest because of its role in...
Myeloid differentiation primary response gene 88 (MYD88) encodes a cytosolic adapter protein that plays an essential role in innate and adaptive immune responses. MYD88 protein functions as an essential signal transducer in the interleukin-1 and in Toll-like receptor signaling pathways by acting as an adapter, which regulates the activation of several proinflammatory genes. MYD88 expression has been shown to be a critical factor against parasitic infections conferring resistance to the organisms in which it is expressed. Mice lacking MYD88 expression as detected by flow cytometry and Western blotting using antibodies against MYD88 were found to be more prone to parasitic infections (1).
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Monocyte Chemoattractant Protein (MCP1) is a potent monocyte attractant, is a member of the CC chemokine subfamily. MCP1 exerts its effects through binding to G-protein-coupled receptors on the surface of leukocytes targeted for activation and migration. The role of MCP1 and its receptor, chemokine receptor-2 (CCR2), in monocyte recruitment during infection or under other inflammatory conditions is well known. Recent studies indicate that MCP-1 may play an important role in pulmonary inflammation. In vitro studies show that a number of cell types are capable of producing MCP1 (1). Rat macrophage subpopulations were examined by immunohistochemistry using various anti-rat macrophage monoclonal antibodies. These studies revealed that the main sources of MCP-1 production were alveolar and interstitial macrophages and polymorphonuclear leukocytes in the rat model of bleomycin-induced lung injury (2...
The polycomb group (PcG) protein, enhancer of zeste homolog 2 (EZH2) is a methyl-transferase that plays a key role in transcriptional gene repression. EZH2 is frequently overexpressed in several malignant tumors, and is often associated with advanced disease stage in many solid tumors. Increased EZH2 levels were detected by Western blotting using anti-EZH2 antibodies in human pancreatic cancer cell lines, suggesting aberrant cell growth and invasiveness (1). EZH2 protein was overexpressed in invasive carcinomas compared to benign breast carcinomas as detected by immunohistochemistry using anti-EZH2 antibodies, suggesting a link between EZH2 and high grade and basal tumors (2).
E-cadherin is a calcium-regulated adhesion molecule expressed in most normal epithelial tissues. E-cadherin is also associated with gland formation, stratification, and epithelial polarization, while loss of E-cadherin can cause dedifferentiation and invasiveness in several human carcinomas (1). In a recent study, human breast cancer tissues were stained immunohistochemistry (IHC) by anti- E-Cadherin antibodies. Loss of E-Cadherin expression correlated with the invasiveness of carcinoma (2).
-Immunohistochemistry-NB110-56937-img0002.jpg "Immunohistochemistry: E-Cadherin Antibody")
Similar...
Phosphotyrosine is the phosphorylated version of the amino acid tyrosine, which results from the activation of intracellular protein kinases (e.g. via growth factors) during normal growth and development, well as in transformation and oncogenesis. Phosphorylation of histidine, serine, threonine and tyrosine residues acts as a signaling system to control many cellular signaling pathways. The cellular networks which rely on these signals can be very complex, so phosphorylation often occurs on multiple sites on a given protein. This phosphorylation is reversible, allowing for exquisite regulation and modulation. Phosphotyrosine is one of the most frequent post-translational modifications that regulate protein-protein interaction and enzyme activity in eukaryotic cells.
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Perforin, also known as the pore-forming protein, pfp, is a 70 kD cytolytic protein expressed in the cytoplasmic granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells. It is one of the major effector molecules used by CTL and NK cells to mediate targeted cell killing and lysis, and thus has an important role in the immune response against tumors and virus infections. Perforin is a membrane-disrupting protein that introduces the granzymes into a target cell, causing cytoplasmic protein degredation and eventual apoptosis.
Proliferating Cell Nuclear Antigen (PCNA), also known as the polymerase delta auxiliary protein, is a nuclear protein essential for DNA replication as well as DNA excision and mismatch repair pathways. It has a large role in cell cycle regulation and response of cells to stress. Studies with PCNA antibodies have determined its mechanism of action to be direct binding of downstream signaling molecules such as CDK inhibitor p21, the endonucleases FEN1 and XPG, and DNA cytosine 5-methyltransferase (DNMT1).
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EGF (epidermal growth factor) stimulates differentiation, proliferation and cell growth by binding to its receptor, EGFR. EGF was first discovered in the mouse submandibular gland in 1986 by Stanley Cohen of Vanderbilt University, leading to a Nobel Prize in Physiology and Medicine. Since then, EGF has been found in many tissues of the human body (including urine, saliva, plasma, milk, macrophages and platelets) and has been the subject of intense study in many areas of clinical research due to its many abilities. EGF from the salivary gland has been shown to maintain oro-esophageal and gastric tissue integrity, including healing of ulcers, inhibiting gastric acid secretion and stimulation of DNA synthesis. Low levels of EGF have also been linked to Parkinson’s Disease in the elderly. EGF has been used to study de novo trastuzumab resistant...
Nucleolin is an abundant, 106 kDa nucleolar phosphoprotein that is a major protein in actively dividing cells. The stability of nucleolin is heavily cell proliferation-dependent, as nucleolin antibody studies have shown that degraded forms are relatively abundant in quiescent non-dividing cells, while nonexist in actively dividing cells. This protein plays multifunctional roles in global processes of rDNA transcription, organization, and rRNA processing. Hanakahi, et. al. believe nucleolin is a component of the B-cell-specific transcription factor LR1 through use of nucleolin antibodies (1). Immunoprecipitation with nucleolin antibodies shows in vitro nucleolin binding to the KLF2 transcription factor...
Myosin is a well-known, hexameric molecular motor that is a key cytoskeletal component. It consists of a pair of myosin heavy chain subunits (MHC), a pair of essential myosin light chain subunits (MLC), and a pair of regulatory light chain subunits (RLCs). Non-muscle myosin heavy chain 10 (also known as Myosin-IIB, cellular myosin heavy chain type B, and NMMHCB) is encoded by the MYH10 gene, while non-muscle myosin heavy chain II-A is encoded by the MYH9 gene. Myosin antibodies have been used to characterize variants and isoforms (1,2).
The myeloid differentiation protein MyD88 (myeloid differentiation primary response protein) was originally identified and characterized as a primary upregulated response gene in interleukin-6 mediated myeloid differentiation. Now, MyD88 is known to be an essential cytosolic adaptor protein in the innate and adaptive immune responses controlled by the interleukin-1 signaling pathway, and MyD88 antibodies have shown that it is expressed in many tissues (1).
Studies with MyD88 antibodies have shown that MyD88 directly...
The protein encoded by mTOR (mammalian target of rapamycin), also known as dTOR in Drosophila, belongs to a family of phosphatidylinositol kinase-related kinases. These kinases regulate fundamental processes of cell growth, proliferation, metabolism
, and migration. mTOR is the target for the cell-cycle arrest and immunosuppressive effects of the drug rapamycin. Deregulation of mTOR stimulates an environment favorable for tumor development and progression. mTOR knockout mice are embryonic lethal. Using mTOR antibodies, researchers have shown that mTOR is required for the maturation and differentiation of multiple cell lineages in a mouse knock-in system (1).
Originally identified as autoantigens from a Scleroderma Polymyositis Syndrome patient (1), the Ku protein family consists of nuclear proteins found in eukaryotes. Autoantibodies to both Ku subunits were subsequently found in other autoimmune diseases such as Systemic Lupus Erythematosus. The Ku heterodimer complex consists of Ku70 and Ku80 and is a very versatile protein that regulates a wide range of important and diverse cellular pathways such as DNA repair and DNA replication, telomere maintenance and telomere silencing, chromatin structure, V(D) J recombination, and Bax-mediated programmed cell death through apoptosis.
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Enhancer of Zeste homolog 2 (EZH2) is the methyltransferase enzyme responsible for trimethylating lysine 27 on histone H3 to produce H3K27Me3. EZH2 is a polycomb group protein that is an essential epigenetic regulator that is often found deregulated in a wide variety of malignant cancer types. Using a KMT/EZH2 antibody, researchers have shown that EZH2 is a key regulator in B cell progenitor cells that uses a novel mechanism of IgH rearrangement control not previously known1. Further KMT/EZH2 antibody studies showed that the phosphorylation of EZH2 by the protein kinase Akt suppresses EZH2 methyltransferase...
Epigenetic mechanisms allow distinction between the active and inactive compartments of the genome, allowing proper cell lineage and embryogenesis. The trimethylation of Histone 3 at lysine 4 (H3K4Me3) is a common epigenetic histone modification that occurs in close proximity to nearly two-thirds of human gene promoters, and seems to balance another modification, trimethylation at lysine 27 (H3K27Me3). Researchers have created global histone methylation maps for human ES cells by using an H3K4Me3 antibody for ChIP (chromatin immunoprecipitation) coupled with paired-end ditags sequencing and found that these two modifications work in...
Adiponectin is most well-known for its role in glucose metabolism and fatty acid breakdown. Adiponectin is secreted solely by adipose tissue, and a person with a higher percentage of body fat will express lower levels of Adiponectin. When higher levels of Adiponectin are present, a mouse will show a lack of adipocyte differentiation and a measurable increase in energy expenditure. These factors are of high interest to people studying obesity and diabetes, such as my lab. When Leptin and Adiponectin are coupled, insulin resistance has been shown to be completely reversed in mice. Adiponectin has a direct correlation with diabetics; a diabetic will have much lower levels in their blood stream, and weight loss will increase these levels.
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The neuropeptide and gut hormone Ghrelin is an endogenous ligand for the growth hormone (GH)-secretagogue receptor (GHSR) within the central nervous system. This pathway has received a great deal of attention and heavy study within the last decade because of its large role in numerous physiological processes including feeding and body weight homeostasis (1, 2). In particular, Ghrelin is a key regulator of reward-based eating behavior (2, 3). Specifically, Ghrelin is derived from preproghrelin, which also generates another peptide called obestatin.
Obestatin is an endogenous ligand for the orphan G protein-coupled...
E-Cadherin is a member of the cadherin superfamily and is fundamental player in a wide range of cellular processes such as development, morphology, polarity, migration and tissue integrity. Specifically, E-cadherin is an approximately 100 kDa epithelial cell glycoprotein whose extracellular domain interacts with that of other E-cadherin molecules on adjacent cells to establish cell-cell adhesion. This adhesion is Ca2+-dependent and a variety of interactions have been identified. E-cadherin antibodies have been extensively used in meta-analysis studies and systematic reviews to validate E-cadherin expression as a prognostic indicator and/or marker for breast cancer (infiltrating ductal and invasive lobular types) 1. A related breast cancer study found that immunohistochemistry with E-cadherin antibodies was helpful in...
Connexin 43/GJA1 is a member of the connexin gene family and the most abundant protein component found within gap junctions. Gap junctions are the cell-to-cell contacts that provide direct intercellular communication between cells by regulating back and forth diffusion of low molecular weight molecules. As such, they regulate quite an extensive range of key cellular processes. Connexin 43/GJA1 antibodies are important tools in wound healing studies, as connexin expression changes dramatically in the skin during different stages of wound healing (1, 2). Clinical trials exploiting connexins as the newest and latest promising target for skin wound healing are ongoing (3). Connexin 43/GJA1 has far-reaching potential therapeutic uses in other tissue and cell types.
Transferrin is a protein found in the blood plasma, a glycoprotein that is specific for controlling free iron in the bodies' biological fluids. Transferrin has two binding sites that are specific for very tight and reversible iron binding. The binding of iron to transferrin can be related to pH levels, among other things, with a high binding affinity for a more acidic pH and decreasing levels as the blood pH becomes more basic. This binding affinity is the basis for the transport mechanism of Transferrin. When the protein, attached to iron, encounters a cell with a transferring receptor, it is transported in a vesicle. While traveling in the vesicle, the pH is reduced by hydrogen ion pumps to a more basic level, around 5.5, causing Transferrin to release the iron ions. The receptor is then transported via vesicle back to the cell surface, and the whole process repeats itself.
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