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Product listing: NRF2 (D1Z9C) XP® Rabbit mAb (Alexa Fluor® 488 Conjugate), UniProt ID Q16236 #40969 to SignalSilence® p53 siRNA II, UniProt ID P04637 #6562

$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).

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

Background: One way that growth factors and mitogens effectively promote sustained cell growth and proliferation is by upregulating mRNA translation (1,2). Growth factors and mitogens induce the activation of p70 S6 kinase and the subsequent phosphorylation of the S6 ribosomal protein. Phosphorylation of S6 ribosomal protein correlates with an increase in translation of mRNA transcripts that contain an oligopyrimidine tract in their 5' untranslated regions (2). These particular mRNA transcripts (5'TOP) encode proteins involved in cell cycle progression, as well as ribosomal proteins and elongation factors necessary for translation (2,3). Important S6 ribosomal protein phosphorylation sites include several residues (Ser235, Ser236, Ser240, and Ser244) located within a small, carboxy-terminal region of the S6 protein (4,5).

$303
100 µl
APPLICATIONS
REACTIVITY
Mouse

Application Methods: Western Blotting

Background: Gasdermin D (GSDMD), a member of the gasdermin family that includes GSDMA, GSDMB, and GSMDC, has been reported to have a critical role as a downstream effector of pyroptosis (1,2). Pyroptosis is a lytic type of cell death triggered by inflammasomes, multiprotein complexes assembled in response to pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) that result in the activation of caspase-1 and subsequent cleavage of pro-inflammatory cytokines IL-1β and IL-18 (3). Gasdermin D was identified by two independent groups as a substrate of inflammatory caspases, caspase-1 and caspase-11/4/5, producing two fragments: GSDMD-N and GSDMD-C. Cleavage results in release of an intramolecular inhibitory interaction between the N- and C-terminal domains, allowing the N-terminal fragment GSMDM-N to initiate pyroptosis through the formation of pores on the plasma membrane (4-7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Members of the Toll-like receptor (TLR) family, named for the closely related Toll receptor in Drosophila, play a pivotal role in innate immune responses (1-4). TLRs recognize conserved motifs found in various pathogens and mediate defense responses (5-7). Triggering of the TLR pathway leads to the activation of NF-κB and subsequent regulation of immune and inflammatory genes (4). The TLRs and members of the IL-1 receptor family share a conserved stretch of approximately 200 amino acids known as the Toll/Interleukin-1 receptor (TIR) domain (1). Upon activation, TLRs associate with a number of cytoplasmic adaptor proteins containing TIR domains, including myeloid differentiation factor 88 (MyD88), MyD88-adaptor-like/TIR-associated protein (MAL/TIRAP), Toll-receptor-associated activator of interferon (TRIF), and Toll-receptor-associated molecule (TRAM) (8-10). This association leads to the recruitment and activation of IRAK1 and IRAK4, which form a complex with TRAF6 to activate TAK1 and IKK (8,11-14). Activation of IKK leads to the degradation of IκB, which normally maintains NF-κB in an inactive state by sequestering it in the cytoplasm.

Molecular Weight:804.03 g/mol

Background: The calcium dependent protein phosphatase calcineurin is responsible for the de-phosphorylation of the transcriptional regulator nuclear factor of activated T cells (NFAT) and is essential for NFAT’s nuclear translocation and activation (1,2). Calcineurin is a target of two common immunosuppressants, cyclosporin A (CsA) (3) and FK-506 (also know as tacrolimus and fugimycin) (4), both of which can inhibit antigen and mitogen triggered T cell activation. These drugs interact with the immunophilins cyclophilin and FKBP-12, respectively, and the immunophilin-drug complex binds to calcineurin to inhibit substrate binding (5). FK-506 can be up to 100-fold more potent than CsA in various models (6-8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Integrins are α/β heterodimeric cell surface receptors that play a pivotal role in cell adhesion and migration, as well as in growth and survival (1,2). The integrin family contains at least 18 α and 8 β subunits that form 24 known integrins with distinct tissue distribution and overlapping ligand specificities (3). Integrins not only transmit signals to cells in response to the extracellular environment (outside-in signaling), but also sense intracellular cues to alter their interaction with the extracellular environment (inside-out signaling) (1,2).

$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. The antibody is expected to exhibit the same species cross-reactivity as the unconjugated Phospho-PLCγ1 (Ser1248) (D25A9) Rabbit mAb #8713.
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse

Application Methods: Flow Cytometry

Background: Phosphoinositide-specific phospholipase C (PLC) plays a significant role in transmembrane signaling. In response to extracellular stimuli such as hormones, growth factors, and neurotransmitters, PLC hydrolyzes phosphatidylinositol 4,5-bisphosphate (PIP2) to generate two secondary messengers: inositol 1,4,5-triphosphate (IP3) and diacylglycerol (DAG) (1). At least four families of PLCs have been identified: PLCβ, PLCγ, PLCδ, and PLCε. Phosphorylation is one of the key mechanisms that regulate the activity of PLC. PLCγ is activated by both receptor and non-receptor tyrosine kinases (2). PLCγ forms a complex with EGF and PDGF receptors, which leads to the phosphorylation of PLCγ at Tyr771, 783, and 1248 (3). Phosphorylation by Syk at Tyr783 activates the enzymatic activity of PLCγ1 (4). PLCγ2 is engaged in antigen-dependent signaling in B cells and collagen-dependent signaling in platelets. Phosphorylation by Btk or Lck at Tyr753, 759, 1197, and 1217 is correlated with PLCγ2 activity (5,6).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Double stranded DNA breaks (DSB’s) are the most toxic of DNA lesions. They occur in response to genotoxic stress, and they are also an obligate intermediate in the V(D)J recombination events in the immune system. The mechanism by which cells deal with DSB’s is known as NHEJ (non-homologous end-joining), and involves a core group of proteins that includes Ku, DNA-PK, XRCC4, and XLF (1). XLF, also known as Cernunnos, was originally discovered as a mutated protein from cells of individuals who displayed features of growth retardation, microcephaly, and immunodeficiency (2). These cells were sensitive to ionizing radiation and defective in V(D)J recombination. Exogenous expression of wild type XLF corrected these deficiencies (3), indicating that XLF is a critical component of the NHEJ response. XLF physically interacts with and may stimulate the ligase activity of XRCC4 (3).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: The 25 kDa synaptosome-associated protein (SNAP25) is a target membrane soluble, N-ethylmaleimide-sensitive factor attachment protein receptor (t-SNARE) that is found on neuronal presynaptic membranes. SNAP25 forms a core complex with the SNARE proteins syntaxin and synaptobrevin to mediate synaptic vesicle fusion with the plasma membrane during Ca2+-dependent exocytosis (1). This complex is responsible for exocytosis of the neurotransmitter γ-aminobutyric acid (GABA). Neurotransmitter release is inhibited by proteolysis of SNAP25 by botulinum toxins A and E (2). SNAP25 plays a secondary role as a Q-SNARE involved in endosome fusion; the protein is associated with genetic susceptibility to attention-deficit hyperactivity disorder (ADHD) (3).

$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 rat cells. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated GSK-3β (D5C5Z) XP® Rabbit mAb #12456.
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Flow Cytometry

Background: Glycogen synthase kinase-3 (GSK-3) was initially identified as an enzyme that regulates glycogen synthesis in response to insulin (1). GSK-3 is a ubiquitously expressed serine/threonine protein kinase that phosphorylates and inactivates glycogen synthase. GSK-3 is a critical downstream element of the PI3K/Akt cell survival pathway whose activity can be inhibited by Akt-mediated phosphorylation at Ser21 of GSK-3α and Ser9 of GSK-3β (2,3). GSK-3 has been implicated in the regulation of cell fate in Dictyostelium and is a component of the Wnt signaling pathway required for Drosophila, Xenopus, and mammalian development (4). GSK-3 has been shown to regulate cyclin D1 proteolysis and subcellular localization (5).

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunohistochemistry (Paraffin), Western Blotting

Background: Tau is a heterogeneous microtubule-associated protein that promotes and stabilizes microtubule assembly, especially in axons. Six isoforms with different amino-terminal inserts and different numbers of tandem repeats near the carboxy terminus have been identified, and tau is hyperphosphorylated at approximately 25 sites by Erk, GSK-3, and CDK5 (1,2). Phosphorylation decreases the ability of tau to bind to microtubules. Neurofibrillary tangles are a major hallmark of Alzheimer's disease; these tangles are bundles of paired helical filaments composed of hyperphosphorylated tau. In particular, phosphorylation at Ser396 by GSK-3 or CDK5 destabilizes microtubules. Furthermore, research studies have shown that inclusions of tau are found in a number of other neurodegenerative diseases, collectively known as tauopathies (1,3).

$269
100 µl
APPLICATIONS
REACTIVITY
Human

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

Background: Also known as plakoglobin, γ-catenin is a member of the Armadillo family of signaling molecules, which includes β-catenin and the Drosophila protein armadillo (1). This family of proteins is involved in Wnt signaling, which is important in embryonic development and in tumorigenesis (2-3). Although the two vertebrate proteins β- and γ-catenin display sequence homology, γ-catenin likely plays a role distinct from that of β-catenin (1, 4-6). γ-catenin localizes to desmosomes and adherens junctions, both sites of intercellular adhesion, and interacts with the cytoplasmic domains of classical and desmosomal cadherins. Interaction of γ- or β-catenin with α-catenin, desmoplakin and other junction proteins provides a link between intercellular junctions and the actin and intermediate filament cytoskeleton. Maintenance and/or modification of this link is vital for control of cell adhesion and migration (1). γ-catenin is modified by phosphorylation, affecting both adhesion and β-catenin dependent transcription (7), and by and O-glycosylation, affecting adhesion (8). Recent evidence suggests that γ-catenin regulates desmosomal adhesion in response to growth factor stimulation (9).

$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 cytometry and immunofluorescent analysis in human cells.
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry

Background: The p53 tumor suppressor protein plays a major role in cellular response to DNA damage and other genomic aberrations. Activation of p53 can lead to either cell cycle arrest and DNA repair or apoptosis (1). p53 is phosphorylated at multiple sites in vivo and by several different protein kinases in vitro (2,3). DNA damage induces phosphorylation of p53 at Ser15 and Ser20 and leads to a reduced interaction between p53 and its negative regulator, the oncoprotein MDM2 (4). MDM2 inhibits p53 accumulation by targeting it for ubiquitination and proteasomal degradation (5,6). p53 can be phosphorylated by ATM, ATR, and DNA-PK at Ser15 and Ser37. Phosphorylation impairs the ability of MDM2 to bind p53, promoting both the accumulation and activation of p53 in response to DNA damage (4,7). Chk2 and Chk1 can phosphorylate p53 at Ser20, enhancing its tetramerization, stability, and activity (8,9). p53 is phosphorylated at Ser392 in vivo (10,11) and by CAK in vitro (11). Phosphorylation of p53 at Ser392 is increased in human tumors (12) and has been reported to influence the growth suppressor function, DNA binding, and transcriptional activation of p53 (10,13,14). p53 is phosphorylated at Ser6 and Ser9 by CK1δ and CK1ε both in vitro and in vivo (13,15). Phosphorylation of p53 at Ser46 regulates the ability of p53 to induce apoptosis (16). Acetylation of p53 is mediated by p300 and CBP acetyltransferases. Inhibition of deacetylation suppressing MDM2 from recruiting HDAC1 complex by p19 (ARF) stabilizes p53. Acetylation appears to play a positive role in the accumulation of p53 protein in stress response (17). Following DNA damage, human p53 becomes acetylated at Lys382 (Lys379 in mouse) in vivo to enhance p53-DNA binding (18). Deacetylation of p53 occurs through interaction with the SIRT1 protein, a deacetylase that may be involved in cellular aging and the DNA damage response (19).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: CCT2 is one of eight largely unrelated subunit proteins found in a protein chaperone complex known as the chaperonin-containing TCP-1 (CCT) or TRiC complex. The CCT complex is an abundanct cytoslic component that is credited with helping newly synthesized polypeptides adopt the correct conformation (1). Proteins that fold and assemble with the help of CCT include the cytoskeletal proteins actin and tubulin as well as up to 15% of newly synthesized eukaryotic proteins (2). CCT2 is the β-subunit of the chaperone complex and is one of several CCT proteins that exhibit increased expression in response to stress. This implies that the CCT complex helps cells recover from protein damage by assisting in protein folding and assembly (3). CCT subunit levels also change throughout the cell cycle, with lower proteins levels (and reduced chaperone activity) found during induced cell cycle arrest during at M phase (4). Each CCT subunit is thought to perform a specific function during protein folding and assembly (5); CCT2 exhibits both actin and tubulin binding activities (6,3) but the exact molecular function on this subunit remains uncertain.

$262
3 nmol
300 µl
SignalSilence® β-Catenin siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit β-catenin expression using RNA interference, a method whereby gene expression can be selectively silenced through the delivery of double stranded RNA molecules into the cell. All SignalSilence® siRNA products from CST are rigorously tested in-house and have been shown to reduce target protein expression by western analysis.
REACTIVITY
Human

Background: β-Catenin is a key downstream effector in the Wnt signaling pathway (1). It is implicated in two major biological processes in vertebrates: early embryonic development (2) and tumorigenesis (3). CK1 phosphorylates β-catenin at Ser45. This phosphorylation event primes β-catenin for subsequent phosphorylation by GSK-3β (4-6). GSK-3β destabilizes β-catenin by phosphorylating it at Ser33, Ser37, and Thr41 (7). Mutations at these sites result in the stabilization of β-catenin protein levels and have been found in many tumor cell lines (8).

$348
100 µl
This Cell Signaling Technology antibody is conjugated to the carbohydrate groups of horseradish peroxidase (HRP) via its amine groups. The HRP conjugated antibody is expected to exhibit the same species cross-reactivity as the unconjugated PKM2 (D78A4) XP® Rabbit mAb #4053.
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Western Blotting

Background: Pyruvate kinase is a glycolytic enzyme that catalyses the conversion of phosphoenolpyruvate to pyruvate. In mammals, the M1 isoform (PKM1) is expressed in most adult tissues (1). The M2 isoform (PKM2) is an alternatively spliced variant of M1 that is expressed during embryonic development (1). Research studies found that cancer cells exclusively express PKM2 (1-3). PKM2 is shown to be essential for aerobic glycolysis in tumors, known as the Warburg effect (1). When cancer cells switch from the M2 isoform to the M1 isoform, aerobic glycolysis is reduced and oxidative phosphorylation is increased (1). These cells also show decreased tumorigenicity in mouse xenografts (1). Recent studies showed that PKM2 is not essential for all tumor cells (4). In the tumor model studied, PKM2 was found to be active in the non-proliferative tumor cell population and inactive in the proliferative tumor cell population (4).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: The 26S proteasome is a highly abundant proteolytic complex involved in the degradation of ubiquitinated substrate proteins. It consists largely of two sub-complexes, the 20S catalytic core particle (CP) and the 19S/PA700 regulatory particle (RP) that can cap either end of the CP. The CP consists of two stacked heteroheptameric β-rings (β1-7) that contain three catalytic β-subunits and are flanked on either side by two heteroheptameric α-rings (α1-7). The RP includes a base and a lid, each having multiple subunits. The base, in part, is composed of a heterohexameric ring of ATPase subunits belonging to the AAA (ATPases Associated with diverse cellular Activities) family. The ATPase subunits function to unfold the substrate and open the gate formed by the α-subunits, thus exposing the unfolded substrate to the catalytic β-subunits. The lid consists of ubiquitin receptors and DUBs that function in recruitment of ubiquitinated substrates and modification of ubiquitin chain topology (1,2). Other modulators of proteasome activity, such as PA28/11S REG, can also bind to the end of the 20S CP and activate it (1,2).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Western Blotting

Background: SLC1A4, also known as ASCT1, is a neutral amino acid transporter. Its other name, ASCT1, was given because it mediates obligatory exchange of alanine, serine, cysteine, and threonine (1). SLC1A4 mediates the efflux of glutamate from the neuron into the synaptic junction via calcium-independent release, as well as mediating the efflux of L-serine from glial cells and its uptake by neurons (2). SLC1A4-mediated transport is shown to involve a symmetrical potassium-independent electroneutral exchange of neutral amino acids and sodium, such that the current activated during transport is carried only by chloride ions (3).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry), Immunoprecipitation, Western Blotting

Background: Cadherins are a superfamily of transmembrane glycoproteins that contain cadherin repeats of approximately 100 residues in their extracellular domain. Cadherins mediate calcium-dependent cell-cell adhesion and play critical roles in normal tissue development (1). The classic cadherin subfamily includes N-, P-, R-, B-, and E-cadherins, as well as about ten other members that are found in adherens junctions, a cellular structure near the apical surface of polarized epithelial cells. The cytoplasmic domain of classical cadherins interacts with β-catenin, γ-catenin (also called plakoglobin), and p120 catenin. β-catenin and γ-catenin associate with α-catenin, which links the cadherin-catenin complex to the actin cytoskeleton (1,2). While β- and γ-catenin play structural roles in the junctional complex, p120 regulates cadherin adhesive activity and trafficking (1-4). Investigators consider E-cadherin an active suppressor of invasion and growth of many epithelial cancers (1-3). Research studies indicate that cancer cells have upregulated N-cadherin in addition to loss of E-cadherin. This change in cadherin expression is called the "cadherin switch." N-cadherin cooperates with the FGF receptor, leading to overexpression of MMP-9 and cellular invasion (3). Research studies have shown that in endothelial cells, VE-cadherin signaling, expression, and localization correlate with vascular permeability and tumor angiogenesis (5,6). Investigators have also demonstrated that expression of P-cadherin, which is normally present in epithelial cells, is also altered in ovarian and other human cancers (7,8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Homer1, Homer2 and Homer3 are scaffolding proteins, composed of an EVH protein–binding domain, a coiled-coil domain and a leucine zipper domain. The EVH domain is a protein-protein binding module that binds to the proline-rich motifs PPXXF, PPXF, and LPSSP of G protein–coupled receptors (GPCRs), inositol 1,4,5-triphosphate (IP3) receptors (IP3Rs), ryanodine receptors, and TRP channels (1-2). The coiled-coil and the leucine zipper domains cause multimerization of Homers and assemble signaling proteins complexes. The Homer1 gene encodes a short isoform (Homer1a, aa 1-186) and two long isoforms (Homer1b, aa 1-354; Homer1c, aa 1-366). Homer1a lacks the coiled-coil domain and leucine zipper, antagonizing multimerization of Homers and thus disassembling signaling proteins complexes (3).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: RANTES/CCL5 (regulated upon activation, T cell expressed and secreted) is a member of the "C-C" or β family of chemokines that induce inflammation and are associated with a number of inflammatory disorders (1,2). RANTES is produced and secreted mainly by CD8+ T cells, macrophages, and platelets, as well as epithelial cells, fibroblasts and some solid tumors (2-7). RANTES acts as a chemoattractant and has other regulatory functions on a number of cell types including monocytes, memory T cells, NK cells, eosinophils, basophils, dendritic cells, and mast cells (3, 7-9). Signaling by RANTES is mediated by several G-protein coupled receptors (GPCRs), including CCR1, CCR3, CCR4 and CCR5.

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Macrophage-colony stimulating factor (M-CSF, CSF-1) receptor is an integral membrane tyrosine kinase encoded by the c-fms proto-oncogene. M-CSF receptor is expressed in monocytes (macrophages and their progenitors) and drives growth and development of this blood cell lineage. (1-3). Binding of M-CSF to its receptor induces receptor dimerization, activation, and autophosphorylation of cytoplasmic tyrosine residues used as docking sites for SH2-containing signaling proteins (4). There are at least five major tyrosine autophosphorylation sites. Tyr723 (Tyr721 in mouse) is located in the kinase insert (KI) region. Phosphorylated Tyr723 binds the p85 subunit of PI3 kinase as well as PLCγ2 (5). Phosphorylation of Tyr809 provides a docking site for Shc (5). Overactivation of this receptor can lead to a malignant phenotype in various cell systems (6). The activated M-CSF receptor has been shown to be a predictor of poor outcome in advanced epithelial ovarian carcinoma (7) and breast cancer (8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Chromatin IP, Immunoprecipitation, Western Blotting

Background: Transducing β-like protein 1 (TBL1X/TBL1) and TBL1-related protein 1 (TBL1XR1/TBLR1) were originally identified as subunits of the co-repressor silencing mediator for retinoic and thyroid hormone receptor (SMRT) and nuclear receptor co-repressor (NCoR) complexes (1-3). These two factors are required for the exchange of co-repressor complexes for co-activators by acting as adaptors to recruit the ubiquitin/proteasome machinery that degrades the co-repressor proteins during ligand mediated activation of transcription (4,5). Co-factor exchange driven by TBL1X/TBL1 and TBL1XR1/TBLR1 appears to be the mechanism by which c-Jun and NF-κB mediated transcription is activated and is therefore likely to be the mechanism employed by other signal-dependent transcription factors as well (4,6). In addition, both TBL1X/TBL1 and TBL1XR1/TBLR1 have essential roles in regulating the Wnt-signaling pathway by recruiting β-catenin to Wnt target genes to activate transcription. Depletion of TBL1X-TBL1XR1 significantly inhibited Wnt-beta-catenin- induced gene expression and oncogenic growth in vitro and in vivo (7). Research studies have shown that upregulation of TBL1XR/TBLR1 is observed in a variety of solid tumors, and is correlated with advanced tumor stage, metastasis and poor prognosis (1).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Microtubule associated proteins regulate the stability of microtubules and control processes such as cell polarity/differentiation, neurite outgrowth, cell division and organelle trafficking (1). The MARK (MAP/microtubule affinity-regulating kinases) family (MARK1-4) of serine/threonine kinases was identified based on their ability to phosphorylate microtubule-associated proteins (MAPs) including tau, MAP2 and MAP4 (2-6). MARK proteins phosphorylate MAPs within their microtubule binding domains, causing dissociation of MAPs from microtubules and increased microtubule dynamics (2-4). In the case of tau, phosphorylation has been hypothesized to contribute to the formation of neurofibrillary tangles observed in Alzheimer's disease. Overexpression of MARK leads to hyperphosphorylation of MAPs, morphological changes and cell death (4). The tumor suppressor kinase LKB1 phosphorylates MARK and the closely related AMP-kinases within their T-loops, leading to increased activity (7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Immunoprecipitation, Western Blotting

Background: Cytosolic phospholipase A2 (cPLA2) is a ubiquitously distributed enzyme that catalyzes the hydrolysis of the sn-2 acyl bond of glycerolipids to produce lysophospholipids and release arachidonic acid (1). cPLA2 has been implicated in diverse cellular responses such as mitogenesis, differentiation, inflammation and cytotoxicity (1). Calcium binding to the amino-terminal CalB domain of cPLA2 promotes the translocation of cPLA2 from cytosol to membrane, where cPLA2 cleaves arachidonic acid from natural membrane (2). Phosphorylation of cPLA2 by MAPK (p42/44 and p38) at Ser505 (3,4) and Ser727 (5) stimulates its catalytic activity.

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Western Blotting

Background: Macrophage-colony stimulating factor (M-CSF, CSF-1) receptor is an integral membrane tyrosine kinase encoded by the c-fms proto-oncogene. M-CSF receptor is expressed in monocytes (macrophages and their progenitors) and drives growth and development of this blood cell lineage. (1-3). Binding of M-CSF to its receptor induces receptor dimerization, activation, and autophosphorylation of cytoplasmic tyrosine residues used as docking sites for SH2-containing signaling proteins (4). There are at least five major tyrosine autophosphorylation sites. Tyr723 (Tyr721 in mouse) is located in the kinase insert (KI) region. Phosphorylated Tyr723 binds the p85 subunit of PI3 kinase as well as PLCγ2 (5). Phosphorylation of Tyr809 provides a docking site for Shc (5). Overactivation of this receptor can lead to a malignant phenotype in various cell systems (6). The activated M-CSF receptor has been shown to be a predictor of poor outcome in advanced epithelial ovarian carcinoma (7) and breast cancer (8).

$115
100 µl
This Cell Signaling Technology antibody is conjugated to phycoerythrin (PE) and tested in-house for direct flow cytometry analysis in human cells.
APPLICATIONS

Application Methods: Flow Cytometry

Background: Isotype control antibodies are used to estimate the nonspecific binding of target primary antibodies due to Fc receptor binding or other protein-protein interactions. An isotype control antibody should have the same immunoglobulin type and be used at the same concentration as the test antibody.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

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

Background: IRAP (also known as LNPEP) was originally described as an insulin-responsive aminopeptidase found in Glut4-containing vesicles (1). It is essentially always in the same compartments as Glut4 and has identical insulin-stimulated translocation patterns as Glut4 (2). IRAP is therefore considered to be a surrogate marker for Glut4 (2). IRAP was later found to be a critical enzyme that regulates the expression and activity of several essential hormones and regulatory proteins, including the Glut4 transporter (3,4). This membrane associated, zinc-dependent cystinyl aminopeptidase acts as both a receptor for angiotensin IV as well as the enzyme that catalyzes the synthesis of this essential hormone from its angiotensinogen precursor (5). IRAP catalyzes the hydrolysis of several peptide hormones, including oxytocin and vasopressin (4). Abnormal IRAP expression or activity is associated with several forms of cancer in humans, including renal and endometrial cancers (6,7).

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Human

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

Background: The inhibitor of apoptosis protein (IAP) family consists of an evolutionarily conserved group of apoptosis inhibitors containing a conserved 70 amino acid BIR (baculovirus inhibitor repeat) domain (1,2). Human members of this family include c-IAP1, c-IAP2, XIAP, survivin, livin, and NAIP. Overexpression of IAP family members, particularly survivin and livin, in cancer cell lines and primary tumors suggests an important role for these proteins in cancer progression (3-5). In general, the IAP proteins function through direct interactions to inhibit the activity of several caspases, including caspase-3, caspase-7, and caspase-9 (5,6). In addition, binding of IAP family members to the mitochondrial protein Smac blocks their interaction with caspase-9, thereby allowing the processing and activation of the caspase (2).

$262
3 nmol
300 µl
SignalSilence® p53 siRNA from Cell Signaling Technology (CST) allows the researcher to specifically inhibit p53 expression using RNA interference, a method whereby gene expression can be selectively silenced through the delivery of double stranded RNA molecules into the cell. All SignalSilence® siRNA products are rigorously tested in-house and have been shown to reduce target protein expression by western analysis.
REACTIVITY
Human

Background: The p53 tumor suppressor protein plays a major role in cellular response to DNA damage and other genomic aberrations. Activation of p53 can lead to either cell cycle arrest and DNA repair or apoptosis (1). p53 is phosphorylated at multiple sites in vivo and by several different protein kinases in vitro (2,3). DNA damage induces phosphorylation of p53 at Ser15 and Ser20 and leads to a reduced interaction between p53 and its negative regulator, the oncoprotein MDM2 (4). MDM2 inhibits p53 accumulation by targeting it for ubiquitination and proteasomal degradation (5,6). p53 can be phosphorylated by ATM, ATR, and DNA-PK at Ser15 and Ser37. Phosphorylation impairs the ability of MDM2 to bind p53, promoting both the accumulation and activation of p53 in response to DNA damage (4,7). Chk2 and Chk1 can phosphorylate p53 at Ser20, enhancing its tetramerization, stability, and activity (8,9). p53 is phosphorylated at Ser392 in vivo (10,11) and by CAK in vitro (11). Phosphorylation of p53 at Ser392 is increased in human tumors (12) and has been reported to influence the growth suppressor function, DNA binding, and transcriptional activation of p53 (10,13,14). p53 is phosphorylated at Ser6 and Ser9 by CK1δ and CK1ε both in vitro and in vivo (13,15). Phosphorylation of p53 at Ser46 regulates the ability of p53 to induce apoptosis (16). Acetylation of p53 is mediated by p300 and CBP acetyltransferases. Inhibition of deacetylation suppressing MDM2 from recruiting HDAC1 complex by p19 (ARF) stabilizes p53. Acetylation appears to play a positive role in the accumulation of p53 protein in stress response (17). Following DNA damage, human p53 becomes acetylated at Lys382 (Lys379 in mouse) in vivo to enhance p53-DNA binding (18). Deacetylation of p53 occurs through interaction with the SIRT1 protein, a deacetylase that may be involved in cellular aging and the DNA damage response (19).