Imgenex

Peptide-affinity Purified Polyclonal Antibody to RAD17

imgenex — Mon, 25 Jul 2011 10:12:32 +0000

Rad17, also known as ‘cell cycle checkpoint protein RAD17,’ is a nuclear protein belonging to the Rad17/RAD24 family and necessary for sustained cell growth, maintenance of chromosomal stability, and ATR-dependent checkpoint activation upon DNA damage. Rad17 is known to have a weak ATPase activity and is required for binding to chromatin and also participates in the recruitment of the RAD1-RAD9-HUS1 complex onto chromatin, and in CHEK1 activation. It may also serve as a sensor of DNA replication progression, and may be involved in homologous recombination. Rad17 is a part of a DNA-binding complex containing RFC2, RFC3, RFC4 and RFC5. Four isoforms have been reported by X-ray irradiation. Overexpression of this protein is seen in various cancer cell lines and in colon carcinoma.

Antigen
A portion of human Rad17 protein containing a phosphorylated serine residue at position 645 was used as the immunogen. This product is antibody from the nonphosphorylated fraction of the immune response.

Application Notes

The amino acid sequence used as immunogen is 100% homologous in human (isoforms CRA_a, CRA_f and CRA_d), rhesus monkey, chimpanzee and orangutan, 92% homologous in horse, cow and mouse and 85% homologous in dog and rat.

Polyclonal Antibody to SNAI2

imgenex — Mon, 25 Jul 2011 10:09:57 +0000

Researchers have indicated that they want access to novel target antibodies quickly to aid in their research. IMGENEX is therefore pleased to be able to offer researchers access to products that are not fully characterized or validated. IMGENEX IMX antibodies are shown by Peptide ELISA to bind to the peptide used as immunogen. Investigators should empirically determine the suitability of the antibody, including optimal dilutions, for other applications of interest.

We cannot guarantee that the IMX antibody will work in any application other than in a Peptide ELISA against the peptide used as immunogen and therefore can not offer a refund if the antibody does not work in your application.
IMX antibodies are offered at a lower price compared to more highly validated antibodies.
We are not able to provide the peptide used as immunogen for IMX antibodies.

As IMX antibodies are not fully validated we appreciate your feedback. Customer feedback is used to help generate testing methodologies which can lead to further product validation or withdrawal.
Zinc finger transcription factor SNAI2/SNAIL2/Slug is found to have some functional significance in formation of axis and mesoderm in Drosophila. SNAIL2 and Twist act as negative regulators of level of Cerberus RNA, which encodes a Nodal, bone morphogenic protein (BMP) and WNT inhibitor. mRNA levels of SNAI2 are regulated by NF-kappaB in early embryo. Partial functional redundancy between Twist, SNAI2 and SNAI1 may be developmentally and physiologically significant given their roles in the induction and progression of various forms of epithelial–mesenchymal transition and the metastasis of cancer cells, the regulation of apoptosis, and their ability to generate stem cell like behaviors in immortalized human epithelial cells.

Antigen
Amino acids 82-100 (SLGRVSPPPPSDTSSKDHS) of human SNAI2 were used as the immunogen.

Polyclonal Antibody to MIB2

imgenex — Mon, 25 Jul 2011 10:08:05 +0000

We cannot guarantee that the IMX antibody will work in any application other than in a Peptide ELISA against the peptide used as immunogen and therefore can not offer a refund if the antibody does not work in your application.
IMX antibodies are offered at a lower price compared to more highly validated antibodies.
We are not able to provide the peptide used as immunogen for IMX antibodies.

As IMX antibodies are not fully validated we appreciate your feedback. Customer feedback is used to help generate testing methodologies which can lead to further product validation or withdrawal.
E3 ubiquitin-protein ligase MIB2 is both a Notch Signaling Pathway and Ubl conjugation pathway protein. It contains nine ANK repeats, two MIB/HERC2 domains, two RING-type zinc fingers and one ZZ-type zinc finger. MIB2 protein has an E3 ubiquitin ligase activity in its C-terminal RING domain and interacts with Xenopus Delta (XD) via the N-terminal region. MIB2 is also able to ligate ubiquitin to XD and shift the membrane localization of Delta to intracellular vesicles. MIB2 rescues both the neuronal and vascular defects in the zebrafish mib (ta52b) mutants. It is also reported that MIB2 acts sequentially in myoblast fusion and sacromeric stability by two separable processes.

Antigen
Amino acids 115-131 of human MIB2 DQGTRTNYRAGYQGAHD protein were used as the immunogen.

Polyclonal Antibody to FBXO9/F-box protein 9

imgenex — Mon, 25 Jul 2011 10:05:50 +0000

We cannot guarantee that the IMX antibody will work in any application other than in a Peptide ELISA against the peptide used as immunogen and therefore can not offer a refund if the antibody does not work in your application.
IMX antibodies are offered at a lower price compared to more highly validated antibodies.
We are not able to provide the peptide used as immunogen for IMX antibodies.

As IMX antibodies are not fully validated we appreciate your feedback. Customer feedback is used to help generate testing methodologies which can lead to further product validation or withdrawal.
F-box only protein 9 is a Ubl conjugation pathway protein and it contains one F-box domain and one TPR repeat. FBXO9 may act as a potential sepsis biomarker or therapeutic target. The F-box proteins constitute one of the four subunits of the ubiquitin protein ligase complex called SCFs (SKP1-cullin-F-box), which functions in phosphorylation-dependent ubiquitination.

Antigen
Amino acids 8-25 CHSDADRVGDEGNESPAE of mouse FBXO9 protein were used as the immunogen.

Polyclonal Antibody to DTX1

imgenex — Mon, 25 Jul 2011 10:03:33 +0000

We cannot guarantee that the IMX antibody will work in any application other than in a Peptide ELISA against the peptide used as immunogen and therefore can not offer a refund if the antibody does not work in your application.
IMX antibodies are offered at a lower price compared to more highly validated antibodies.
We are not able to provide the peptide used as immunogen for IMX antibodies.

As IMX antibodies are not fully validated we appreciate your feedback. Customer feedback is used to help generate testing methodologies which can lead to further product validation or withdrawal.
Protein deltex-1 is a Notch Signaling Pathway protein which belongs to the Deltex Family of proteins. It contains one RING-type zinc finger and two WWE domains. DTX1 acts as regulator of Notch signaling and has functional significance in cell-fate determinations. It mediates the antineural activity of Notch by inhibiting the transcriptional activation mediated by MATCH1. It is involved in neurogenesis, lymphogenesis, myogenesis and MZB (Marginal Zone B) cell differentiation. It promotes B-cell development at the expense of T-cell development, suggesting that it can antagonize NOTCH1. It functions as an ubiquitin ligase protein in vitro, suggesting that it may regulate the Notch pathway via some ubiquitin ligase activity. DTX1, along with DTX2 and DTX3, functions as E3 ligases based on their capacity for self ubiquitination.

Antigen
Amino acids 583-599 KTEFGSNLTGHGYPDAS of human DTX1 protein were used as the immunogen.

Apoptosis Programmed Cell Death

imgenex — Mon, 01 Oct 2007 04:17:41 +0000

Coined in the 1960′s,apoptosis is derived from the Greek word apopiptein which means to fall off from. Apoptosis can be induced by a number of stimuli including UV damage, irradiation, drug treatment, or tumor necrosis factor. Once induced, apoptosis can, in turn, act through a number of different cell death signaling pathways.

The number of apoptosis and ‘programmed cell death’ related kits and reagents available to the market have increased significantly over the last few years. This is in large part the result of increasing evidence implicating the role of apoptosis in a number of significantly relevant disease processes including certain autoimmune diseases, transplantation rejection, and neurodegenerative diseases. IMGENEX offers over 200 Apoptosis related antibodies, as well as ELISA kits, caspase inhibitors, active caspase detection kits, apoptosis detection kits, and mitochondrial permeability detection kits.

Regulatory T Cells (Treg)

imgenex — Mon, 01 Oct 2007 04:09:25 +0000

Early development and differentiation of nascent T cells that migrate from bone marrow to become mature, naïve T cells, which are capable of responding to antigen takes place inside the thymus. Around 10¹⁰TCR (T cell receptor) variations are generated in developing T lymphocyte clones through a random process of somatic cell gene reorganization. During this process, often T-cells recognizing self-antigens are generated. Due to the ability of these self-reactive T-cells to elicit an autoimmune attack, they are permanently removed by the thymus through negative selection and clonal deletion. But, some of them manage to escape the thymic defenses and harbor themselves in the peripheral lymphoid organs. In periphery, T lymphocytes undergo further differentiation into effectors of various immune functions.

One of many immunotolerance mechanisms that immune system has developed to distinguish between self and non-self antigens is regulatory T cells or Tregs. These cells are recently characterized specialized T-cell subsets that actively suppress a variety of immune responses. Researchers have broadly classified Tregs into natural and adaptive Tregs. Natural Tregs are CD4⁺CD25⁺T-cells that originate in the thymus and play a significant role in immune homeostasis and protection against autoimmunity. Adaptive Tregs are non-regulatory CD4⁺T-cells that have up-regulated CD25 expression during pathological and inflammatory conditions such as cancers and infections.

Although the principal immunosuppressive mechanism of Tregs remains elusive, several in vivo experimental models have indicated that Tregs secrete large amounts of immunosuppressants including IL-9, IL-10 and TGF-β upon activation. These lymphokines are capable of inhibiting activation of Th1, Th2 cells and CTLs required for cell-mediated immunity, inflammation and antibody production. Certain recent experimental data and results even indicate that IL-2-IL-2R signaling is vital for development, maintenance, survival, expansion and suppressive activity of Tregs. Increased expression of certain other characteristic markers including CTLA-4, glucocorticoid-inducible tumor necrosis factor receptor (GITR) and OX40 has been identified on Tregs whose function inside these cells is still not clear. The TCRs displayed on Tregs are capable of recognizing and interacting with any peptide-MHC class II ligand having certain range of avidity. But, the contribution of TCR signaling and role of TCR-ligand interactions towards regulatory T-cell development needs to be determined.

Several elegant experiment using transgenic mice and retrovirus mediate over expression studies, researchers have identified FoxP3, a transcription factor, to be a specific molecular marker essential for the development and function of Tregs. The primary evidence regarding the involvement of FoxP3 in the development of Tregs was provided by the experiments of Sakaguchi et al, (ref ?) in patients suffering from IPEX, a rare and fatal human autoimmune disorder. In these patients, mutated FoxP3 gene causes improper development of Tregs resulting in hyperactivation of T-cells reactive to self-antigens. Recently, experiments have clearly shown that retroviral mediated introduction of FoxP3 into conventional CD4+ T-cells converts them into regulatory T-cells.

The emergence of regulatory T-cells and role of FoxP3 as a critical player in the negative control of a of various normal and pathological immune responses holds great promise for the development of novel therapies useful for the treatment of autoimmune diseases in humans. However, there are several questions that remain to be answered including the basic biology of the Tregs, various ligands responsible for thymic selection of these cells, the exact function of FoxP3 in relation with various markers present on Tregs and most importantly, the mechanisms by which Tregs exert their suppressive effects. A better understanding of manipulating FoxP3 and Tregs would enable us to harness the tremendous therapeutic potential in various clinical situations including Type I diabetes, Multiple sclerosis, GVHD, rheumatoid arthritis, allergy, and cancers.

Actin Antibody Available in Imgenex now

imgenex — Mon, 01 Oct 2007 04:03:27 +0000

Actin is a ubiquitous protein involved in the formation of filaments that are major components of the cytoskeleton. It is the monomeric subunit of microfilaments, one of the three major components of the cytoskeleton, and of thin filaments which are part of the contractile apparatus in muscle cells. It is the most abundant protein in the typical eukaryotic cell, accounting for about 15% in some cell types. The protein is highly conserved, and forms a huge variety of structure in cells in concert with a huge numbers of actin binding proteins. The actin filaments interact with myosin to produce a sliding effect, which is the basis of muscular contraction and many aspects of cell motility, including cytokinesis. The individual subunits of actin are known as globular actin (G-actin) that assembles into long filamentous polymers called F-actin. Two parallel F-actin strands twist around each other in a helical formation, giving rise to microfilaments of the cytoskeleton. Microfilaments measure approximately 7 nm in diameter with a loop of the helix repeating every 37nm. Each actin protomer binds one molecule of ATP and has one high affinity site for either calcium or magnesium ions, as well as several low affinity sites. It exists as a monomer in low salt concentrations, but filaments form rapidly as salt concentration rises, with the consequent hydrolysis of ATP. Actin from many sources forms a tight complex with deoxyribonuclease (DNase I) although the significance of this is still unknown. The formation of this complex results in the inhibition of DNase I activity, and actin loses its ability to polymerise. It has been shown that an ATPase domain of actin shares similarity with ATPase domains of hexokinase and hsp70 proteins. In vertebrates there are three groups of actin isoforms: alpha, beta and gamma. The alpha actins are found in muscle tissues and are a major constituent of the contractile apparatus. The beta and gamma actins co-exist in most cell types as components of the cytoskeleton and as mediators of internal cell motility. MreB, a major component of the bacterial cytoskeleton, exhibitshigh structural homology to its eukaryotic counterpart actin. Further it has been suggested that members of the Rho family of small guanosine triphosphatases have emerged as key regulators of the actin cytoskeleton, and through their interaction with multiple target proteins, they ensure coordinated control of other cellular activities such as gene transcription and adhesion.

Reference:

Actin isoforms. Curr Opin Cell Biol. 1993 Feb;5(1):48-55 Herman IM
The assembly of MreB, a prokaryotic homolog of actin. The assembly of MreB, a prokaryotic homolog of actin. J Biol Chem. 2005 Jan 28;280(4):2628-35. Epub 2004 Nov 16
Rho GTPases and the Actin Cytoskeleton Science 23 January 1998:
Vol. 279. no. 5350, pp. 509 – 514 Alan Hall

Akt Family: Antibodies from Imgenex

imgenex — Mon, 01 Oct 2007 03:59:05 +0000

Akt family of serine/threonine-directed kinases regulatesa diverse array of biological processes, including cellularsurvival, proliferation, glucose homeostasis, and vasculartone and are important molecules in mammalian cellular signaling. Thethree widely expressed isoforms of PKB (PKB, PKBß andPKB; also known as Akt1, Akt2 and Akt3, respectively) are each composedof an N-terminal PtdIns(3,4,5)P₃- and PtdIns(3,4)P₂-bindingPH domain and a C-terminal kinase catalytic domain. Stimulation by numerous growth factors, cytokines, hormones and neurotransmitters can activate PKB/Akt in a phosphoinositide 3-kinase-dependent manner. Through receptor tyrosine kinases, these stimuli cause phosphoinositide 3-kinase activation, and generation of the membrane phospholipid PtdIns(3,4,5)P3. PtdIns(3,4,5)P3 then recruits PKB/Akt to the membrane, where it becomes phosphorylated (for PKBa/Akt1) by upstream kinases, phosphoinositide-dependent kinase 1. Followingthe activation of PI 3-kinase, PKB isoforms are recruited fromthe cytosol to the plasma membrane through their interactionwith PtdIns(3,4,5)P₃ and/or PtdIns(3,4)P₂ where they are thoughtto undergo a conformational change and become activated by phosphorylationof two residues. PKB can promote cell survival by inhibiting proteins that mediate apoptosis. Phosphorylation of BADby PKB (and other AGC kinases) enables it to interact with 14-3-3proteins, which prevents it from binding to Bcl-X_L and therebysuppresses apoptosis. It directly phosphorylate and inhibit the caspase proteasesm, key executioners of apoptosis. PKBbeta, an essential genefor the maintenance of normal glucose homeostasis and is likely to represent a critical intermediatein the insulin signal transduction pathway. PKBactivation might inhibit apoptosis by promoting the increasedexpression of survival molecules or the degradation of pro-apoptotic molecules. PKB also phosphorylates and activates endothelial nitric oxidesynthase, thereby promoting angiogenesis (formation of new bloodvessels). Inhibition of GSK3 following its phosphorylation by PKB hasalso been suggested to play a role in inhibiting apoptosis inneuronal cells. Thus it plays a key role in cancer progression by stimulating cellproliferation and inhibiting apoptosis, which suggests it, likely to be a hot drug target for the treatmentof cancer, diabetes and stroke.

ATM (Ataxia Telangiectasia Mutated) Antibodies from Imgenex

imgenex — Mon, 01 Oct 2007 03:54:26 +0000

ATM, the gene product mutated in the cancer susceptibility syndrome ataxia–telangiectasia, is related to proteins involved in DNA repair and cell-cycle control. It encodes a nuclear 350 kDa phosphoprotein containing a carboxy terminus phosphatidylinositol 3-kinase (Pl-3 kinase) catalytic domain shared by members of a superfamily of large eukaryotic proteins involved in intracellular signaling, DNA-damage induced cell cycle checkpoints, DNA repair and recombination. It was discovered as mutated proteins in patients with ataxia-telagiectasia (A-T), a severe genetic disorder characterized by cerebellar degeneration, neuromotor dysfunction, chromosomal instability, immune system defects, cancer predisposition, and acute sensitivity to ionizing radiations. In undamaged cells it is present as a dimer or oligomer molecule in which the kinase domain is silent because associated with the FAT region of another ATM monomer. Following DSB formation, it rapidly autophosphorylates on residue Serine 1981, and the inactive ATM dimers are converted (dissociated) into active ATM monomers. Active phosphorylated ATM molecules interact and phosphorylate downstream proteins that affect one or more of the cell cycle checkpoints. Some of the known substrates are the p53 protein and its ubiquitin ligase, MDM2; the Nbs1 protein; the Brca1 protein, which interacts with other repair proteins; the checkpoint kinase 2, Chk2; the Rad17 protein and the chromatin remodeling protein SMC1. Phylogenetic analyses reveal that the ATM protein is most closely related to several very large proteins that define a subgroup of the PI 3-kinase family which include the Schizosaccharomyces pombe Rad3 protein and its probable Saccharomyces cerevisiae homologue, Mec1p/Esr1p. Other proteins in the ATM family are S. cerevisiae Tor1p and Tor2p and their mammalian counterpart FRAP, which function, at least in part, by controlling progression through the G1 phase of the cell cycle. The ATM gene provides instructions for making a protein that is located primarily in the nucleus of cells, where it helps control the rate at which cells grow and divide and also assists cells in recognizing damaged or broken strands of DNA. It has been suggested that it acts as a lipid kinase, and feeds the phosphorylated lipids into signaling pathways to regulate cell-cycle progression or the activity of DNA-repair components. It regulates NF-κB activity and control the transcription of many genes that play important roles in the development and function of the immune system. In the DNA-damage response pathway, it acts upstream of p53 to induce cell cycle arrest at the G1/S and G2/M boundaries and a slowing of the S-phase. Signalling by ATM involves interactions with and phosphorylation of critical molecules, including the mitotic checkpoints Chk1 and Chk2. Apart from its role in ataxia telangiectasia (AT), ATM gene mutations have also been found in T-cell prolymphocytic leukaemia patients with no family history of AT and in non-Hodgkin’s lymphomas.