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Product listing: EI24 (D3F6Z) Rabbit mAb, UniProt ID O14681 #42328 to Tri-Methyl-Histone H3 (Lys27) (C36B11) Rabbit mAb (PE Conjugate), UniProt ID P68431 #40724

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Etoposide-induced 2.4 mRNA (EI24)/p53-induced gene 8 (PIG8) was identified as a DNA damage response gene induced by etoposide in a p53 dependent manner with roles in growth suppression and apoptosis (1-3). As a pro-apoptotic gene, some evidence suggests that EI24 functions as a tumor suppressor gene in cases such as breast and cervical cancer (4-6). The mechanism of EI24 is still unclear, but studies have shown that it can localize to the endoplasmic reticulum and associate with Bcl-2 and could regulate apoptosis through regulation of Bcl-2 function (7). Liver-specific deletions of EI24 in mice show impaired autophagic flux, suggesting that it may also play a role in regulating basal autophagy (8). EI24 was shown to be involved in the autophagic degradation of many RING E3 ligases (9). In addition, decreased expression of EI24 in epithelial tumor cells induced epithelial-to-mesenchymal transition (EMT) (10). Together these studies suggest multiple mechanisms for EI24 to regulate tumor progression that includes regulation of apoptosis, autophagy, and EMT.

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting

Background: The sodium-dependent phosphate transport protein 2B (NaPi-2b, SLC34A2) is a sodium dependent inorganic phosphate (Pi) transporter that regulates phosphate homeostasis in various organs, including the small intestine, lung, liver, and testis (1). In the small intestine, NaPi-2b localizes to the intestinal brush border membrane to mediate Pi reabsorption (2). In the lung, NaPi-2b is expressed in the apical membrane of type II alveolar cells and is involved in the synthesis of surfactant (3). Mutations in the corresponding SLC34A2 gene causes pulmonary alveolar microlithiasis, a rare autosomal recessive disorder characterized by the deposition of calcium phosphate microliths throughout the lungs (4). Research studies show aberrant expression of NaPi-2b in various type of cancer, including ovarian, breast, and lung cancer (5). Chromosomal rearrangements involving SLC34A2-ROS1 are seen in gastric carcinoma and non-small cell lung cancer and result in the formation of a SLC34A2-ROS1 chimeric protein that retains a constitutive kinase activity (6,7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Cytoplasmic 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS1) catalyzes the first committed step of mevalonate pathway essential for cholesterol biosynthesis (1). HMGCS1 transcription is regulated by sterol levels (2). Studies showed that miR-223 reduces cholesterol biosynthesis by inhibiting HMGCS1 and methylsterol monooxygenase 1 (3). In addition, activation of the EGFR family member ERBB4 induces the expression of SREBP-regulated genes (including HMGCS1) involved in cholesterol biosynthesis, suggesting a role of this enzyme in the metabolic re-programming in ERBB4-driven cancers (4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Clusterin (CLU, apolipoprotein J) is a multifunctional glycoprotein that is expressed ubiquitously in most tissues. Clusterin functions as a secreted chaperone protein that interacts with and stabilizes stress-induced proteins to prevent their precipitation (1,2). Research studies show that clusterin plays a protective role in Alzheimer’s disease by sequestering amyloid β(1-40) peptides to form long-lived, stable complexes, which prevents amyloid fibril formation (3-5).In addition to the secreted protein, several intracellular isoforms are localized to the nucleus, mitochondria, cytoplasm, and ER. The subcellular distribution of these multiple isoforms leads to the diversity of clusterin functions. Additional studies report that clusterin is involved in membrane recycling, cell adhesion, cell proliferation, apoptosis, and tumor survival (6-9). The clusterin precursor is post-translationally cleaved into the mature clusterin α and clusterin β forms. Clusterin α and β chains create a heterodimer through formation of disulfide bonds (10).

$305
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 700 fluorescent dye and tested in-house for direct flow cytometry analysis in human cells transfected with Myc-tagged protein.
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry

Background: Epitope tags are useful for the labeling and detection of proteins using immunoblotting, immunoprecipitation, and immunostaining techniques. Because of their small size, they are unlikely to affect the tagged protein’s biochemical properties.

$303
100 µl
REACTIVITY
Human

Background: Estrogen receptor α (ERα), a member of the steroid receptor superfamily, contains highly conserved DNA binding and ligand binding domains (1). Through its estrogen-independent and estrogen-dependent activation domains (AF-1 and AF-2, respectively), ERα regulates transcription by recruiting coactivator proteins and interacting with general transcriptional machinery (2). Phosphorylation at multiple sites provides an important mechanism to regulate ERα activity (3-5). Ser104, 106, 118, and 167 are located in the amino-terminal transcription activation function domain AF-1, and phosphorylation of these serine residues plays an important role in regulating ERα activity. Ser118 may be the substrate of the transcription regulatory kinase CDK7 (5). Ser167 may be phosphorylated by p90RSK and Akt (4,6). According to the research literature, phosphorylation at Ser167 may confer tamoxifen resistance in breast cancer patients (4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Immunoprecipitation, Western Blotting

Background: The polycomb group (PcG) proteins are involved in maintaining the silenced state of multiple developmentally regulated genes and contribute to the maintenance of cell identity, cell cycle regulation, and oncogenesis. Enhancer of zest homolog 1 (Ezh1), is a member of this large protein family and a subunit of the polycomb repressor complex 2 (PRC2), also containing SUZ12 and EED. Ezh1 and its paralog Ezh2 are mutually exclusive catalytic subunits of the PRC2 complex, which functions to mono-, di-, and tri-methylated Lys27 on histone H3, a mark that is associated with transcriptional repression. While EZH1 is less abundant than EZH2, it is still required for cell identity and self-renewal of embryonic stem cells (1,2). Ezh1 is also required for hematopoietic stem cell maintenance and functions to prevent a senescence-like cell cycle arrest (3). Ezh1 is required for myogenic differentiation and hepatocyte homeostasis and regeneration (4,5). While many studies have implicated Ezh2 in multiple types of cancer, a potential role for Ezh1 is less understood. However, several studies have shown dual inhibitors of Ezh1/Ezh2 to be more effective than Ezh2-specific inhibitors in treatment of multiple myeloma, prostate cancer, diffuse large B-cell lymphoma, and leukemia, suggesting an important role for Ezh1 in cancer (6-8).

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting

Background: ABCG2 (BCRP1/ABCP/MXR) is a member of the ATP-binding cassette transporter family that functions as ATP-dependent transporters for a wide variety of chemical compounds and are associated with drug-resistance in cancer cells (1-6). ABCG2 is a heavily glycosylated transmembrane protein with six transmembrane spanning regions consistent with it functioning as a half-transporter. The ABC family can exist as either full-length transporters or as half-transporters that form functional transporters through homo- or heterodimerization. High expression of ABCG2 was found in placenta as well as cell lines selected for resistance to a number of chemotherapeutic drugs, including mitoxantrone, doxorubicin, topotecan and flavopiridol. In rodents, the highest expression of ABCG2 was found in kidney (8). ABCG2 expression has also been observed in stem cell populations, particularly in hematopoietic and neuronal stem cells and is downregulated with differentiation (9-12).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Ring1 and YY1-binding protein (RYBP) is a widely expressed nuclear protein that functions as a modulator of Ring1A/Ring1B-dependent histone H2A monoubiquitylation (1-3). Ring1A and Ring1B proteins function as the catalytic core subunits of polyclomb repressor complex 1 (PRC1), which acts to repress gene expression in part through monoubiquitination of histone H2A on Lys119 (4). By binding to both the YY1 DNA-binding transcription factor and Ring1A/Ring1B, RYPB is able to recruit the PRC1 complex to target loci independent of prior tri-methylation of histone H3 Lys27 by the EZH2-dependent PRC2 complex (2,3). RYBP also binds monoubiquitinated H2A Lys119 and may act to stabilize or spread binding of PRC1 across large domains of repressed chromatin (5). In addition, RYBP directly stimulates the ubiquitination activity of Ring1A/Ring1B and is required for proper differentiation of stem cells along multiple cell lineages (2,3,6,7). RYBP has also been shown to bind MDM2 and block ubiquitination and degradation of p53, leading to cell cycle arrest and apoptosis in response to DNA damage (8). Many studies demonstrate that RYBP functions as a tumor suppressor protein. RYBP expression is decreased in multiple cancers, including non-small cell lung cancer, hepatocellular carcinoma, and glioblastoma with decreased expression correlating with metastasis and poor prognosis (8-11).

$327
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 488 fluorescent dye and tested in-house for direct flow cytometric analysis in human cells. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated Phospho-p38 MAP Kinase (Thr180/Tyr182) (3D7) Rabbit mAb #9215.
APPLICATIONS
REACTIVITY
D. melanogaster, Human, Monkey, Mouse, Pig, Rat, S. cerevisiae

Application Methods: Flow Cytometry

Background: p38 MAP kinase (MAPK), also called RK (1) or CSBP (2), is the mammalian orthologue of the yeast HOG kinase that participates in a signaling cascade controlling cellular responses to cytokines and stress (1-4). Four isoforms of p38 MAPK, p38α, β, γ (also known as Erk6 or SAPK3), and δ (also known as SAPK4) have been identified. Similar to the SAPK/JNK pathway, p38 MAPK is activated by a variety of cellular stresses including osmotic shock, inflammatory cytokines, lipopolysaccharide (LPS), UV light, and growth factors (1-5). MKK3, MKK6, and SEK activate p38 MAPK by phosphorylation at Thr180 and Tyr182. Activated p38 MAPK has been shown to phosphorylate and activate MAPKAP kinase 2 (3) and to phosphorylate the transcription factors ATF-2 (5), Max (6), and MEF2 (5-8). SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-imidazole) is a selective inhibitor of p38 MAPK. This compound inhibits the activation of MAPKAPK-2 by p38 MAPK and subsequent phosphorylation of HSP27 (9). SB203580 inhibits p38 MAPK catalytic activity by binding to the ATP-binding pocket, but does not inhibit phosphorylation of p38 MAPK by upstream kinases (10).

$305
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 647 fluorescent dye and tested in-house for direct flow cytometric analysis in human cells. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated PD-L1 (Extracellular Domain Specific) (D8T4X) Rabbit mAb #86744.
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry)

Background: Programmed cell death 1 ligand 1 (PD-L1, B7-H1, CD274) is a member of the B7 family of cell surface ligands that regulate T cell activation and immune responses. The PD-L1 ligand binds the PD-1 transmembrane receptor and inhibits T cell activation. PD-L1 was discovered following a search for novel B7 protein homologs and was later shown to be expressed by antigen presenting cells, activated T cells, and tissues including placenta, heart, and lung (1-3). Similar in structure to related B7 family members, PD-L1 protein contains extracellular IgV and IgC domains and a short, cytoplasmic region. Research studies demonstrate that PD-L1 is expressed in several tumor types, including melanoma, ovary, colon, lung, breast, and renal cell carcinomas (4-6). Expression of PD-L1 in cancer is associated with tumor infiltrating lymphocytes, which mediate PD-L1 expression through the release of interferon gamma (7). Additional research links PD-L1 expression to cancers associated with viral infections (8,9).

$348
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to phycoerythrin (PE) and tested in-house for direct flow cytometry analysis in human cells. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated p38 MAPK (D13E1) XP® Rabbit mAb #8690.
APPLICATIONS
REACTIVITY
Bovine, Hamster, Human, Monkey, Mouse, Pig, Rat

Application Methods: Flow Cytometry

Background: p38 MAP kinase (MAPK), also called RK (1) or CSBP (2), is the mammalian orthologue of the yeast HOG kinase that participates in a signaling cascade controlling cellular responses to cytokines and stress (1-4). Four isoforms of p38 MAPK, p38α, β, γ (also known as Erk6 or SAPK3), and δ (also known as SAPK4) have been identified. Similar to the SAPK/JNK pathway, p38 MAPK is activated by a variety of cellular stresses including osmotic shock, inflammatory cytokines, lipopolysaccharide (LPS), UV light, and growth factors (1-5). MKK3, MKK6, and SEK activate p38 MAPK by phosphorylation at Thr180 and Tyr182. Activated p38 MAPK has been shown to phosphorylate and activate MAPKAP kinase 2 (3) and to phosphorylate the transcription factors ATF-2 (5), Max (6), and MEF2 (5-8). SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-imidazole) is a selective inhibitor of p38 MAPK. This compound inhibits the activation of MAPKAPK-2 by p38 MAPK and subsequent phosphorylation of HSP27 (9). SB203580 inhibits p38 MAPK catalytic activity by binding to the ATP-binding pocket, but does not inhibit phosphorylation of p38 MAPK by upstream kinases (10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: TRAFs (TNF receptor-associated factors) are a family of multifunctional adaptor proteins that bind to surface receptors and recruit additional proteins to form multiprotein signaling complexes capable of promoting cellular responses (1-3). Members of the TRAF family share a common carboxy-terminal "TRAF domain", which mediates interactions with associated proteins; many also contain amino-terminal Zinc/RING finger motifs. The first TRAFs identified, TRAF1 and TRAF2, were found by virtue of their interactions with the cytoplasmic domain of TNF-receptor 2 (TNFRII) (4). The six known TRAFs (TRAF1-6) act as adaptor proteins for a wide range of cell surface receptors and participate in the regulation of cell survival, proliferation, differentiation, and stress responses.

$327
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 488 fluorescent dye and tested in-house for direct flow cytometric and immunofluorescent analysis in human cells. The antibody is expected to exhibit the same species cross-reactivity as the unconjugated Phospho-STING (Ser366) (D8K6H) Rabbit mAb #40818.
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry)

Background: Stimulator of interferon genes (STING, TMEM173, MITA) is a transmembrane adaptor protein that is a critical component of the cellular innate immune response to pathogenic cytoplasmic DNA (1,2). STING is a ubiquitously expressed protein found predominantly in the ER (1). The enzyme cGAMP synthase (cGAS) produces the second messenger cyclic-GMP-AMP (cGAMP) in response to cytoplasmic DNA (3,4). cGAMP binds and activates STING (3,4). In addition, detection of cytoplasmic DNA by nucleic acid sensors, including DDX41 or IFI16, results in STING activation (5,6). Following activation, STING translocates with TBK1 to perinuclear endosomes (7). The TBK1 kinase phosphorylates and activates interferon regulatory factors (IRFs) and NF-κB, which leads to the induction of type I interferon and other immune response genes (1,2,7).

$364
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to phycoerythrin (PE) and tested in-house for direct flow cytometry analysis in human cells. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated Ubiquityl-Histone H2A (Lys119) (D27C4) XP® Rabbit mAb #8240.
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Flow Cytometry

Background: The nucleosome, made up of four core histone proteins (H2A, H2B, H3, and H4), is the primary building block of chromatin. Originally thought to function as a static scaffold for DNA packaging, histones have now been shown to be dynamic proteins, undergoing multiple types of post-translational modifications, including acetylation, phosphorylation, methylation, and ubiquitination (1). Ubiquitin is a conserved 76 amino acid peptide unit that can be covalently linked to many cellular proteins by the ubiquitination process. Three components are involved in this protein-ubiquitin conjugation process. Ubiquitin is first activated by forming a thioester complex with the activation component E1; the activated ubiquitin is subsequently transferred to the ubiquitin-carrier protein E2, then from E2 to ubiquitin ligase E3 for final delivery to the epsilon-NH2 of the target protein lysine residue (2). Histone H2A is mono-ubiquitinated at Lys119 by the Polycomb Repressor Complex 1 (PRC1) and is critical for transcriptional silencing of the developmental HOX genes and X chromosome inactivation (3-6). PRC1 is composed of Bmi1 and RING1A (also RING1 or RNF1), both of which act to enhance the E3 ubiquitin ligase activity of the catalytic subunit RING1B (also RING2 or RNF2) (3,4). Histone H2A is also mono-ubiquitinated at Lys119 at sites of DNA damage. This mono-ubiquitination event requires the PRC1 components Bmi1 and RING1B, in addition to another E3 ubiquitin ligase RNF8, and contributes to subsequent recruitment of the BRCA1 complex, via binding of RAP80/UIMC1 (ubiquitin interactive motif containing 1 protein) (7-10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: MTHFD2 is a bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase involved in mitochondrial folate metabolism (1). MTHFD2 expression is developmentally regulated, as it is expressed in embryos but not in most adult tissues. Recent research studies have shown that MTHFD2 is consistently overexpressed in many cancer types and correlated with poor survival in breast cancer (2-5). Overexpression of MTHFD2 promotes cell proliferation while its depletion induces cell death in human cancer cells (6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Chromatin IP, Western Blotting

Background: Histones are evolutionarily conserved proteins that play a vital role in the compaction, storage, and regulation of DNA within the eukaryotic nucleus. The basic subunit of chromatin, the nucleosome core particle, is composed of DNA wound around two copies each of the core histone proteins H2A, H2B, H3, and H4 (1-3). Formation of higher order chromatin structure is facilitated through the binding of linker histone H1 to the nucleosome particle (chromatosome) (4-6). In humans and mice, there are 11 distinct histone H1 variants, which include the somatic variants (H1.1, H1.2, H1.3, H1.4, and H1.5) that are expressed ubiquitously, and cell type specific variants such as H1t found in the testis and H1.0 expressed in terminally differentiated cells (6-10). Binding of histone H1 to chromatin limits accessibility of DNA to other proteins by stabilizing nucleosome positioning, competing for binding sites, and limiting the activity of chromatin remodeling proteins such as the SWI/SNF complex (6,11-14). Histone H1 binding is highly dynamic and is thought to be regulated by post-translational modifications (6). For example, cell cycle regulated phosphorylation of histone H1 leads to chromatin condensation and decondensation depending on the site of phosphorylation and histone H1.4 Lys34 acetylation by GCN5 has been linked to increased mobility of H1.4 and transcriptional activation (6, 15-18).

$260
100 µl
APPLICATIONS
REACTIVITY
Mouse

Application Methods: Immunoprecipitation, Western Blotting

Background: Siglec-10 is a sialic acid-binding Ig-like lectin that has been shown to negatively regulate innate and adaptive immune system function (1). Siglec-10 is a type 1 transmembrane protein that has four extracellular Ig-like domains, a transmembrane region, and a cytoplasmic tail with two immunoreceptor tyrosine-based inhibitory motifs (ITIM) (2). Siglec-10 is expressed in dendritic cells (DCs), monocytes, B cells, NK cells, and T cells (2, 3). Siglec-10 interacts with CD24 to suppress immune responses to danger associated molecular patterns (DAMPs) by associating with the tyrosine phosphatase SHP-1, a negative regulator of nuclear factor-kappa B (NF-κB) (4). Siglec-10 has been shown to bind soluble CD52 leading to the impairment of phosphorylation of the T cell receptor–associated kinases Lck and Zap70 and T cell activation (3). It has been proposed that this mechanism of suppression could be involved in T cell homeostasis and the prevention of type I diabetes (3). Siglec-10 has also been identified as the leukocyte ligand for vascular adhesion protein-1 (VAP-1), which plays a key role in leukocyte trafficking (5). Lectin galactoside-binding soluble 3 binding protein (LGALS3BP), a tumor-associated immunomodulatory ligand, has also been shown to bind Siglec-10 (6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: SLK (Ste20-like Kinase) is a member of the germinal center kinase (GCK) family of proteins. SLK has a kinase domain located at the N terminus (1). The autophosphorylation of SLK at Thr183 and Ser189 is required for the upregulation of SLK kinase activity (1, 2). The protein also has a caspase cleavage site DXXD and a SH3 binding site PXXP located in the middle part of its sequence, and a regulatory C terminal coiled-coil domain for homodimerization and adaptor binding (1-4). SLK plays important roles in development, tissue regeneration and cancer cell migration by regulating several signaling pathways (5-7). SLK phosphorylates and activates ASK1 to induce downstream p38 phosphorylation and apoptosis (8,9). During cell cycle, SLK phosphorylates Polo-like kinase (PLK) at Thr210 to promote G2/M transition (10,11). SLK also promotes cell division by direct phosphorylation of ERMs and dynactin to activate microtubule reorganization and spindle orientation (12, 13). During focal adhesion and cell migration process, SLK is activated and colocalized to the focal adhesion complex where it promotes complex turnover by phosphorylating paxillin at Ser250 (14, 15).

$348
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 647 fluorescent dye and tested in-house for direct flow cytometric analysis in human cells. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated BCL6 (D4I2V) XP® Rabbit mAb #14895.
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry

Background: Chromosomal translocations result in misregulation of the proto-oncogene BCL6 in patients with B cell-derived non-Hodgkin's lymphoma (1). The BCL6 gene is selectively expressed in mature B cells and encodes a nuclear phosphoprotein that belongs to the BTB/POZ zinc finger family of transcription factors (2,3). BCL6 protein can bind to target DNA sequences of Stat6 and, analogous to Stat6, modulate the expression of interleukin-4-induced genes (4). Furthermore, BCL6 restrains p53-dependent senescence, making BCL6-active tumors functionally p53-negative (5). The mitogen-activated protein kinases, Erk1 and Erk2, but not JNK, phosphorylate BCL6 at multiple sites. Phosphorylation of BCL6 at Ser333 and Ser343 results in degradation of BCL6 by the ubiquitin/proteasome pathway in B cells (6,7). In addition, BCL6 is acetylated and its transcriptional repressor function is inhibited by the transcriptional co-activator p300 (8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Molecule interacting with CasL protein 1 (MICAL1) is a Protein-methionine sulfoxide oxidase. MICAL1 can bind directly to F-actin and oxidize specific methionine residues to promote actin filament disassembly (1-3). MICAL1 is an important component of semaphorin signaling cascades that has effects on cell movement, angiogenesis, immunology, diabetes, and cancer (4-7). MICAL1 binds to NDR1/2 and antagonizes MST1-induced NDR activation and apoptosis (8).

$348
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 700 fluorescent dye and tested in-house for direct flow cytometric analysis in human cells. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated ALK (D5F3®) XP® Rabbit mAb #3633.
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry

Background: Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor for pleiotrophin (PTN), a growth factor involved in embryonic brain development (1-3). In ALK-expressing cells, PTN induces phosphorylation of both ALK and the downstream effectors IRS-1, Shc, PLCγ, and PI3 kinase (1). ALK was originally discovered as a nucleophosmin (NPM)-ALK fusion protein produced by a translocation (4). Investigators have found that the NPM-ALK fusion protein is a constitutively active, oncogenic tyrosine kinase associated with anaplastic lymphoma (4). Research literature suggests that activation of PLCγ by NPM-ALK may be a crucial step for its mitogenic activity and involved in the pathogenesis of anaplastic lymphomas (5).A distinct ALK oncogenic fusion protein involving ALK and echinoderm microtubule-associated protein like 4 (EML4) has been described in the research literature from a non-small cell lung cancer (NSCLC) cell line, with corresponding fusion transcripts present in some cases of lung adenocarcinoma. The short, amino-terminal region of the microtubule-associated protein EML4 is fused to the kinase domain of ALK (6-8).

$269
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunofluorescence (Immunocytochemistry), Immunohistochemistry (Paraffin), Immunoprecipitation, Western Blotting

Background: The matrix metalloproteinases (MMPs) are a family of proteases that target many extracellular proteins including other proteases, growth factors, cell surface receptors, and adhesion molecules (1). Among the family members, MMP-2, MMP-3, MMP-7, and MMP-9 have been characterized as important factors for normal tissue remodeling during embryonic development, wound healing, tumor invasion, angiogenesis, carcinogenesis, and apoptosis (2-4). Research studies have shown that MMP activity correlates with cancer development (2). One mechanism of MMP regulation is transcriptional (5). Once synthesized, MMP exists as a latent proenzyme. Maximum MMP activity requires proteolytic cleavage to generate active MMPs by releasing the inhibitory propeptide domain from the full length protein (5).

$348
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 488 fluorescent dye and tested in-house for direct flow cytometric analysis in mouse cells. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated NRF2 (D1Z9C) XP® Rabbit mAb #12721.
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse

Application Methods: Flow Cytometry

Background: The nuclear factor-like 2 (NRF2) transcriptional activator binds antioxidant response elements (ARE) of target gene promoter regions to regulate expression of oxidative stress response genes. Under basal conditions, the NRF2 inhibitor INrf2 (also called KEAP1) binds and retains NRF2 in the cytoplasm where it can be targeted for ubiquitin-mediated degradation (1). Small amounts of constitutive nuclear NRF2 maintain cellular homeostasis through regulation of basal expression of antioxidant response genes. Following oxidative or electrophilic stress, KEAP1 releases NRF2, thereby allowing the activator to translocate to the nucleus and bind to ARE-containing genes (2). The coordinated action of NRF2 and other transcription factors mediates the response to oxidative stress (3). Altered expression of NRF2 is associated with chronic obstructive pulmonary disease (COPD) (4). NRF2 activity in lung cancer cell lines directly correlates with cell proliferation rates, and inhibition of NRF2 expression by siRNA enhances anti-cancer drug-induced apoptosis (5).

$364
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 647 fluorescent dye and tested in-house for direct flow cytometric analysis in human cells. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated Phospho-SLP-76 (Ser376) (D7S1K) XP® Rabbit mAb #92711.
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry

Background: SH2 domain-containing leukocyte protein of 76 kDa (SLP-76) is a hematopoietic adaptor protein that is important in multiple biochemical signaling pathways and necessary for T cell development and activation (1). ZAP-70 phosphorylates SLP-76 and LAT as a result of TCR ligation. SLP-76 has amino-terminal tyrosine residues followed by a proline rich domain and a carboxy-terminal SH2 domain. Phosphorylation of Tyr113 and Tyr128 result in recruitment of the GEF Vav and the adapter protein Nck (2). TCR ligation also leads to phosphorylation of Tyr145, which mediates an association between SLP-76 and Itk, which is accomplished in part via the proline rich domain of SLP-76 and the SH3 domain of ITK (3). Furthermore, the proline rich domain of SLP-76 binds to the SH3 domains of Grb2-like adapter Gads (3,4). In resting cells, SLP-76 is predominantly in the cytosol. Upon TCR ligation, SLP-76 translocates to the plasma membrane and promotes the assembly of a multi-protein signaling complex that includes Vav, Nck, Itk and PLCγ1 (1). The expression of SLP-76 is tightly regulated; the protein is detected at very early stages of thymocyte development, increases as thymocyte maturation progresses, and is reduced as cells mature to CD4+ CD8+ double-positive thymocytes (5).

$269
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: IHC-Leica® Bond™, Immunohistochemistry (Paraffin), Western Blotting

Background: CD40, also known as tumor necrosis factor receptor superfamily member 5 (TNFRSF5), is a type I transmembrane protein expressed on the surface of B cells and professional antigen-presenting cells of the immune system, as well as on several non-hematopoietic cell types and cancers (1-4). CD40 interacts with CD40 ligand (CD40L/TNFSF5), which is expressed primarily on activated T cells but has also been reported on blood platelets, mast cells, basophils, NK cells, and B cells (5). Upon engagement with CD40L, CD40 signals through TNF receptor associated factors and MAP kinase signaling pathways, resulting in a wide variety of immune and inflammatory responses, including dendritic cell activation and cross-presentation, T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation (6-8). The CD40/CD40L axis is essential for the initiation and progression of cellular and humoral adaptive immunity, and is an important area of interest in the study of tumor immunology, neurodegenerative diseases, vascular diseases, and inflammatory disorders (9-12).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry)

Background: Stimulator of interferon genes (STING, TMEM173, MITA) is a transmembrane adaptor protein that is a critical component of the cellular innate immune response to pathogenic cytoplasmic DNA (1,2). STING is a ubiquitously expressed protein found predominantly in the ER (1). The enzyme cGAMP synthase (cGAS) produces the second messenger cyclic-GMP-AMP (cGAMP) in response to cytoplasmic DNA (3,4). cGAMP binds and activates STING (3,4). In addition, detection of cytoplasmic DNA by nucleic acid sensors, including DDX41 or IFI16, results in STING activation (5,6). Following activation, STING translocates with TBK1 to perinuclear endosomes (7). The TBK1 kinase phosphorylates and activates interferon regulatory factors (IRFs) and NF-κB, which leads to the induction of type I interferon and other immune response genes (1,2,7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: TNFRSF8/CD30 is a type-I transmembrane glycoprotein that is a member of the TNFR superfamily. CD30 is synthesized as a precursor protein that undergoes extensive posttranslational modification before becoming embedded in the plasma membrane as a 120-kDa transmembrane protein (1,2). The expression of CD30 is upregulated in activated T-cells and may trigger costimulatory signaling pathways upon its engagement (3,4). While its expression is normally restricted to subsets of activated T-cells and B-cells, CD30 expression is robustly upregulated in hematologic malignancies, such as Hodgkin’s lymphoma (HL), anaplastic large cell lymphoma (ALCL), and adult T-cell leukemia, thus making it an attractive target for therapeutic intervention (5,6). Research studies have suggested that in certain disease contexts, CD30 recruits TRAF2 and TRAF5 adaptor proteins to drive NF-kappa B activation, aberrant cell growth, and cytokine production (7-9). CD30 signaling is also regulated by TACE-dependent proteolytic cleavage of its ectodomain, which results in reduced CD30L-dependent activation of CD30+ cells (10, 11).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Tuberin is a product of the TSC2 tumor suppressor gene and an important regulator of cell proliferation and tumor development (1). Mutations in either TSC2 or the related TSC1 (hamartin) gene cause tuberous sclerosis complex (TSC), an autosomal dominant disorder characterized by development of multiple, widespread non-malignant tumors (2). Tuberin is directly phosphorylated at Thr1462 by Akt/PKB (3). Phosphorylation at Thr1462 and Tyr1571 regulates tuberin-hamartin complexes and tuberin activity (3-5). In addition, tuberin inhibits the mammalian target of rapamycin (mTOR), which promotes inhibition of p70 S6 kinase, activation of eukaryotic initiation factor 4E binding protein 1 (4E-BP1, an inhibitor of translation initiation), and eventual inhibition of translation (3,6,7).

$327
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to phycoerythrin (PE) and tested in-house for direct flow cytometry analysis in human cells. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated Tri-Methyl-Histone H3 (Lys27) (C36B11) Rabbit mAb #9733.
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Flow Cytometry

Background: The nucleosome, made up of four core histone proteins (H2A, H2B, H3, and H4), is the primary building block of chromatin. Originally thought to function as a static scaffold for DNA packaging, histones have now been shown to be dynamic proteins, undergoing multiple types of post-translational modifications, including acetylation, phosphorylation, methylation, and ubiquitination (1). Histone methylation is a major determinant for the formation of active and inactive regions of the genome and is crucial for the proper programming of the genome during development (2,3). Arginine methylation of histones H3 (Arg2, 17, 26) and H4 (Arg3) promotes transcriptional activation and is mediated by a family of protein arginine methyltransferases (PRMTs), including the co-activators PRMT1 and CARM1 (PRMT4) (4). In contrast, a more diverse set of histone lysine methyltransferases has been identified, all but one of which contain a conserved catalytic SET domain originally identified in the Drosophila Su(var)3-9, Enhancer of zeste, and Trithorax proteins. Lysine methylation occurs primarily on histones H3 (Lys4, 9, 27, 36, 79) and H4 (Lys20) and has been implicated in both transcriptional activation and silencing (4). Methylation of these lysine residues coordinates the recruitment of chromatin modifying enzymes containing methyl-lysine binding modules such as chromodomains (HP1, PRC1), PHD fingers (BPTF, ING2), tudor domains (53BP1), and WD-40 domains (WDR5) (5-8). The discovery of histone demethylases such as PADI4, LSD1, JMJD1, JMJD2, and JHDM1 has shown that methylation is a reversible epigenetic marker (9).