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Product listing: Phospho-Akt (Ser473) (D9E) XP® Rabbit mAb (Sepharose® Bead Conjugate), UniProt ID P31749 #4070 to SignalSilence® Stat6 siRNA I, UniProt ID P42226 #6358

$364
400 µl
This Cell Signaling Technology (CST) antibody is immobilized via covalent binding of primary amino groups to N-hydroxysuccinimide (NHS)-activated Sepharose® beads. Phospho-Akt (Ser473) (D9E) XP® Rabbit mAb (Sepharose® Bead Conjugate) is useful for immunoprecipitation assays. The unconjugated Phospho-Akt (Ser473) (D9E) XP® Rabbit mAb #4060 reacts with human, mouse, rat, hamster, Drosophila melanogaster, bovine and zebrafish phospho-Akt protein. CST expects that Phospho-Akt (Ser473) (D9E) XP® Rabbit mAb (Sepharose® Bead Conjugate) will also recognize phospho-Akt in these species.
APPLICATIONS
REACTIVITY
Bovine, D. melanogaster, Hamster, Human, Monkey, Mouse, Rat, Zebrafish

Application Methods: Immunoprecipitation

Background: Akt, also referred to as PKB or Rac, plays a critical role in controlling survival and apoptosis (1-3). This protein kinase is activated by insulin and various growth and survival factors to function in a wortmannin-sensitive pathway involving PI3 kinase (2,3). Akt is activated by phospholipid binding and activation loop phosphorylation at Thr308 by PDK1 (4) and by phosphorylation within the carboxy terminus at Ser473. The previously elusive PDK2 responsible for phosphorylation of Akt at Ser473 has been identified as mammalian target of rapamycin (mTOR) in a rapamycin-insensitive complex with rictor and Sin1 (5,6). Akt promotes cell survival by inhibiting apoptosis through phosphorylation and inactivation of several targets, including Bad (7), forkhead transcription factors (8), c-Raf (9), and caspase-9. PTEN phosphatase is a major negative regulator of the PI3 kinase/Akt signaling pathway (10). LY294002 is a specific PI3 kinase inhibitor (11). Another essential Akt function is the regulation of glycogen synthesis through phosphorylation and inactivation of GSK-3α and β (12,13). Akt may also play a role in insulin stimulation of glucose transport (12). In addition to its role in survival and glycogen synthesis, Akt is involved in cell cycle regulation by preventing GSK-3β-mediated phosphorylation and degradation of cyclin D1 (14) and by negatively regulating the cyclin dependent kinase inhibitors p27 Kip1 (15) and p21 Waf1/Cip1 (16). Akt also plays a critical role in cell growth by directly phosphorylating mTOR in a rapamycin-sensitive complex containing raptor (17). More importantly, Akt phosphorylates and inactivates tuberin (TSC2), an inhibitor of mTOR within the mTOR-raptor complex (18,19).

$348
100 µl
This Cell Signaling Technology antibody is conjugated to biotin under optimal conditions. The biotinylated antibody is expected to exhibit the same cross-reactivity as the unconjugated antibody (Jak2 (D2E12) XP® Rabbit mAb #3230).
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Members of the Janus family of tyrosine kinases (Jak1, Jak2, Jak3, and Tyk2) are activated by ligands binding to a number of associated cytokine receptors (1). Upon cytokine receptor activation, Jak proteins become autophosphorylated and phosphorylate their associated receptors to provide multiple binding sites for signaling proteins. These associated signaling proteins, such as Stats (2), Shc (3), insulin receptor substrates (4), and focal adhesion kinase (FAK) (5), typically contain SH2 or other phospho-tyrosine-binding domains.

$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 cytometry analysis in human cells. The antibody is expected to exhibit the same species cross-reactivity as the unconjugated VEGF Receptor 2 (D5B1) Rabbit mAb # 9698.
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Flow Cytometry

Background: Vascular endothelial growth factor receptor 2 (VEGFR2, KDR, Flk-1) is a major receptor for VEGF-induced signaling in endothelial cells. Upon ligand binding, VEGFR2 undergoes autophosphorylation and becomes activated (1). Major autophosphorylation sites of VEGFR2 are located in the kinase insert domain (Tyr951/996) and in the tyrosine kinase catalytic domain (Tyr1054/1059) (2). Activation of the receptor leads to rapid recruitment of adaptor proteins, including Shc, GRB2, PI3 kinase, NCK, and the protein tyrosine phosphatases SHP-1 and SHP-2 (3). Phosphorylation at Tyr1212 provides a docking site for GRB2 binding and phospho-Tyr1175 binds the p85 subunit of PI3 kinase and PLCγ, as well as Shb (1,4,5). Signaling from VEGFR2 is necessary for the execution of VEGF-stimulated proliferation, chemotaxis and sprouting, as well as survival of cultured endothelial cells in vitro and angiogenesis in vivo (6-8).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Highly conserved and widely expressed plastin proteins comprise a subset of actin-binding proteins that include proteins that promote actin bundling. Three plastins exhibiting differential expression are found in mammals and include L-plastin, T-plastin, and I-plastin. T-plastin (plastin-3) is found in cells of most solid tissues, while I-plastin (plastin-1) is expressed specifically in the kidney, colon, and small intestine (1-3). Research studies have shown that L-plastin (plastin-2) or lymphocyte cytosolic protein 1 (LCP1) is mainly expressed in hematopoietic cells and nonhematopoietic tumors, and increased expression correlates with metastatic progression in colon cancer cell lines (4). Investigators have found that overexpression of LCP1 in premetastatic cancer cell lines induces invasion and loss of E-cadherin expression, which is characteristic of metastatic cancer cell lines (5). LCP1 becomes phosphorylated at Ser5 upon stimulation through the T cell receptor/CD3 complex in association with the CD2 cell adhesion molecule or the CD28 receptor (6). Phosphorylation at Ser5 enhances the ability of LCP1 to bind to F-actin and increases cell motility (7,8).

$327
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to phycoerythrin (PE) 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 Di-Methyl-Histone H3 (Lys4) (C64G9) Rabbit mAb #9725.
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).

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Autophagy is a catabolic process for the autophagosomic-lysosomal degradation of bulk cytoplasmic contents (1,2). It is generally activated by conditions of nutrient deprivation but is also associated with a number of physiological processes including development, differentiation, neurodegeneration, infection, and cancer (3). The molecular machinery of autophagy was largely discovered in yeast and is directed by a number of autophagy-related (Atg) genes.Vacuolar trafficking and autophagy are controlled by the class III type phosphoinositide 3-kinase (PI3K) Vps34, which generates phosphoinositide-3-phosphate (PtdIns3P) (4,5). Atg18 and Atg21 are two related WD-repeat proteins that bind PtdIns3P via a conserved Phe-Arg-Arg-Gly motif (6,7). It has been shown that Atg18 binds to Atg2 and that this complex is directed to vacuolar membranes by its interaction with PtdIns3P (8). Human orthologs of Atg18 and Atg21 were identified as members of the WD-repeat protein Interacting with Phosphoinositides (WIPI) family (9-11). WIPI1 (also called WIPI49) and WIPI2 have been shown to translocate from several vacuolar compartments to LC3-positive autophagosomes during autophagy; this translocation may be used as an autophagy marker (12).

$262
3 nmol
300 µl
SignalSilence® LC3B siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit LC3B expression using RNA interference, a method whereby gene expression can be selectively silenced through the delivery of double stranded RNA molecules into the cell. LC3B siRNA I will not inhibit expression of LC3A or LC3C. 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: Autophagy is a catabolic process for the autophagosomic-lysosomal degradation of bulk cytoplasmic contents (1,2). Autophagy is generally activated by conditions of nutrient deprivation, but it has also been associated with a number of physiological processes including development, differentiation, neurodegenerative diseases, infection, and cancer (3). Autophagy marker Light Chain 3 (LC3) was originally identified as a subunit of microtubule-associated proteins 1A and 1B (termed MAP1LC3) (4) and subsequently found to contain similarity to the yeast protein Apg8/Aut7/Cvt5 critical for autophagy (5). Three human LC3 isoforms (LC3A, LC3B, and LC3C) undergo post-translational modifications during autophagy (6-9). Cleavage of LC3 at the carboxy terminus immediately following synthesis yields the cytosolic LC3-I form. During autophagy, LC3-I is converted to LC3-II through lipidation by a ubiquitin-like system involving Atg7 and Atg3 that allows for LC3 to become associated with autophagic vesicles (6-10). The presence of LC3 in autophagosomes and the conversion of LC3 to the lower migrating form, LC3-II, have been used as indicators of autophagy (11).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Eg5 (also called kinesin-like protein 11 or Kif11) belongs to the kinesin-like family of motor proteins important in chromosome positioning, centrosome separation, and mitotic spindle formation. Phosphorylation of Eg5 by mitotic kinases regulates its activity by modulating its association with microtubules (1,2). Because anti-mitotic chemotherapeutic drugs, such as taxanes, target microtubules and have pleiotropic and sometimes toxic effects, drugs that target microtubule-associated proteins such as Eg5 are currently in development (3-5).

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

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

Background: Echinoderm microtubule-associated protein-like 4 (EML4) is a 120 kDa microtubule-associated WD-repeat protein of the echinoderm microtubule-associated protein family (1). The expression of EML4 is necessary for correct intracellular microtubule network formation (2). EML4 protein expression is upregulated during mitosis and downregulated during the remaining cell cycle (1). During mitosis, EML4 is heavily phosphorylated and is associated with the mitotic spindle (2). The amino-terminal segment of EML4 is essential for microtubule association and function.

$293
100 µl
APPLICATIONS
REACTIVITY
Hamster, Human, Monkey, Mouse, Rat

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

Background: According to affinity and function, calcium-binding proteins are separated into two classes: calcium buffers and calcium sensors. Calmodulin is a well-studied calcium sensor with well-established roles in synaptic plasticity. Neuronal calcium-sensor 1 (NCS1) is also a member of the calcium sensor family, however, its role in synaptic plasticity remains under investigation. NCS1 contains multiple EF-hand calcium-binding motifs and an amino-terminal myristoyl group (1). NCS1 has a large number of binding partners. Most of these protein interactions are calcium-dependent (e.g. dopamine D2 receptor), although some are calcium-independent (e.g. IP3 receptor) (2). In murine dentate gyrus, NCS1 promotes synaptic plasticity and rapid acquisition of spatial memory (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 human cells. The antibody is expected to exhibit the same species cross-reactivity as the unconjugated Zap-70 (D1C10E) XP® Rabbit mAb #3165.
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Flow Cytometry

Background: The Syk family protein tyrosine kinase Zap-70 is expressed in T and NK cells and plays a critical role in mediating T cell activation in response to T cell receptor (TCR) engagement (1). Following TCR engagement, Zap-70 is rapidly phosphorylated on several tyrosine residues through autophosphorylation and transphosphorylation by the Src family tyrosine kinase Lck (2-6). Tyrosine phosphorylation correlates with increased Zap-70 kinase activity and downstream signaling events. Expression of Zap-70 is correlated with disease progression and survival in patients with chronic lymphocytic leukemia (7,8).

$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 human cells. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated VISTA (D1L2G™) XP® Rabbit mAb #64953.
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Flow Cytometry

Background: VISTA (V-Domain Ig Suppressor of T Cell Activation) is a negative checkpoint control protein that regulates T cell activation and immune responses. VISTA, which contains a single Ig-like V-type domain, a transmembrane domain, and an intracellular domain, has sequence similarity to both the B7 and CD28 family members. Although primarily expressed by myeloid cells, VISTA is also expressed by CD4+, CD8+, and FoxP3+ T-cells. Thus, VISTA is described as both a ligand and a receptor (1-3). Blocking VISTA induces T-cell activation and proliferation, and potentiates disease severity in the EAE model (1). Furthermore, genetic deletion of VISTA in mice leads to spontaneous T-cell activation and chronic inflammation (4,5). In mouse models of cancer, neutralization of VISTA enhances T-cell proliferation and effector function and increases tumor infiltration, suggesting VISTA blockade could be an effective strategy for tumor immunotherapy (6,7).

$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. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated Acetyl-Histone H4 (Lys16) (E2B8W) Rabbit mAb #13534.
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry)

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 (1,2). Histone acetylation occurs mainly on the amino-terminal tail domains of histones H2A (Lys5), H2B (Lys5, 12, 15, and 20), H3 (Lys9, 14, 18, 23, 27, 36 and 56), and H4 (Lys5, 8, 12, and 16) and is important for the regulation of histone deposition, transcriptional activation, DNA replication, recombination, and DNA repair (1-3). Hyper-acetylation of the histone tails neutralizes the positive charge of these domains and is believed to weaken histone-DNA and nucleosome-nucleosome interactions, thereby destabilizing chromatin structure and increasing the accessibility of DNA to various DNA-binding proteins (4,5). In addition, acetylation of specific lysine residues creates docking sites for a protein module called the bromodomain, which binds to acetylated lysine residues (6). Many transcription and chromatin regulatory proteins contain bromodomains and may be recruited to gene promoters, in part, through binding of acetylated histone tails. Histone acetylation is mediated by histone acetyltransferases (HATs), such as CBP/p300, GCN5L2, PCAF, and Tip60, which are recruited to genes by DNA-bound protein factors to facilitate transcriptional activation (3). Deacetylation, which is mediated by histone deacetylases (HDAC and sirtuin proteins), reverses the effects of acetylation and generally facilitates transcriptional repression (7,8).

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

Application Methods: Western Blotting

Background: α-ketoglutarate dehydrogenase complex is a rate-regulating enzyme in the Krebs Cycle (1). Dihydrolipoamide succinyltransferase (DLST) is a key subunit in this complex (2). Reduction of DLST increases reactive oxygen species production, suggesting its role in oxidative stress (2). Research has shown that deficiency of DLST in mice is linked to increased oxidative stress in mitochondria, a process that may be involved in the pathogenesis of Alzheimer's disease (2).

$348
400 µl
This Cell Signaling Technology antibody is immobilized via covalent binding of primary amino groups to N-hydroxysuccinimide (NHS)-activated Sepharose® beads. Jak2 (D2E12) XP® Rabbit mAb (Sepharose® Bead Conjugate) is useful for the immunoprecipitation of Jak2 proteins.
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation

Background: Members of the Janus family of tyrosine kinases (Jak1, Jak2, Jak3, and Tyk2) are activated by ligands binding to a number of associated cytokine receptors (1). Upon cytokine receptor activation, Jak proteins become autophosphorylated and phosphorylate their associated receptors to provide multiple binding sites for signaling proteins. These associated signaling proteins, such as Stats (2), Shc (3), insulin receptor substrates (4), and focal adhesion kinase (FAK) (5), typically contain SH2 or other phospho-tyrosine-binding domains.

$348
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 488 fluorescent dye and tested in-house for direct immunofluorescent analysis in human cells. This antibody is expected to exhibit the same species cross reactivity as the unconjugated Synapsin-1 (D12G5) XP® Rabbit mAb #5297
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunofluorescence (Frozen)

Background: Synapsins, a group of at least five related members (synapsins Ia, Ib, IIa, IIb, and IIIa), are abundant brain proteins essential for regulating neurotransmitter release (1,2). All synapsins contain a short amino-terminal domain that is highly conserved and phosphorylated by PKA or CaM kinase I (1). Phosphorylation of the synapsin amino-terminal domain at Ser9 inhibits its binding to phospholipids and dissociates synapsins from synaptic vesicles (2).

$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-Smad2 (Ser465/Ser467) (E8F3R) Rabbit mAb #18338.
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Flow Cytometry

Background: Members of the Smad family of signal transduction molecules are components of a critical intracellular pathway that transmit TGF-β signals from the cell surface into the nucleus. Three distinct classes of Smads have been defined: the receptor-regulated Smads (R-Smads), which include Smad1, 2, 3, 5, and 8; the common-mediator Smad (co-Smad), Smad4; and the antagonistic or inhibitory Smads (I-Smads), Smad6 and 7 (1-5). Activated type I receptors associate with specific R-Smads and phosphorylate them on a conserved carboxy terminal SSXS motif. The phosphorylated R-Smad dissociates from the receptor and forms a heteromeric complex with the co-Smad (Smad4), allowing translocation of the complex to the nucleus. Once in the nucleus, Smads can target a variety of DNA binding proteins to regulate transcriptional responses (6-8).

$260
100 µl
APPLICATIONS
REACTIVITY
Mouse, Rat

Application Methods: Western Blotting

Background: Undifferentiated embryonic cell transcription factor 1 (UTF1) is expressed in cells of the inner cell mass and the epiblast (1). Expression is down-regulated with development, although it is maintained in the embryonic germ cells and in the adult gonads (1). Reduced expression in embryonic stem cells (ESCs) is associated with failure to differentiate properly, although self-renewal is unaffected (2). UTF1 is tightly associated with chromatin in mouse and human ESCs and may be involved in maintaining an epigenetic environment necessary for the pluripotent state (2,3). Co-expression of UTF1 with reprogramming factors c-Myc, Oct-4, Sox2 and KLF4, along with siRNA knock-down of p53 increased efficiency of induced pluripotent stem cell generation by 100 fold (4).

$327
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 Acetyl-Histone H4 (Lys16) (E2B8W) Rabbit mAb #13534.
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 (1,2). Histone acetylation occurs mainly on the amino-terminal tail domains of histones H2A (Lys5), H2B (Lys5, 12, 15, and 20), H3 (Lys9, 14, 18, 23, 27, 36 and 56), and H4 (Lys5, 8, 12, and 16) and is important for the regulation of histone deposition, transcriptional activation, DNA replication, recombination, and DNA repair (1-3). Hyper-acetylation of the histone tails neutralizes the positive charge of these domains and is believed to weaken histone-DNA and nucleosome-nucleosome interactions, thereby destabilizing chromatin structure and increasing the accessibility of DNA to various DNA-binding proteins (4,5). In addition, acetylation of specific lysine residues creates docking sites for a protein module called the bromodomain, which binds to acetylated lysine residues (6). Many transcription and chromatin regulatory proteins contain bromodomains and may be recruited to gene promoters, in part, through binding of acetylated histone tails. Histone acetylation is mediated by histone acetyltransferases (HATs), such as CBP/p300, GCN5L2, PCAF, and Tip60, which are recruited to genes by DNA-bound protein factors to facilitate transcriptional activation (3). Deacetylation, which is mediated by histone deacetylases (HDAC and sirtuin proteins), reverses the effects of acetylation and generally facilitates transcriptional repression (7,8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Immunoprecipitation, Western Blotting

Background: The transient receptor potential cation channel subfamily V member 3 (TRPV3 or VRL3) is a widely expressed ligand-gated ion channel protein that acts in temperature detection between 22º C and 40º C (1). Related transient receptor proteins (TRP) respond to different temperature ranges; TRPA1 responds to cold temperatures and TRPM1 to cool, while warmer temperatures elicit response from TRPV3 and TRPV4. Noxious heat or painful temperatures correlate with TRPM8 and TRPV1 activity (reviewed in 2). TRPV3 is found in association with TRPV1 (VR1) and is thought to modulate activity of this noxious heat-responsive protein (3). Increased TRPV1 and TRPV3 protein expression is correlated with nervous injury, while reduced expression of both may be see in cases of diabetic skin neuropathy (2). Recent evidence implicates TRPV3 in pruritic dermatitis, or itching associated with eczema and related skin disorders (4).

$303
100 µl
APPLICATIONS
REACTIVITY
Monkey, Mouse

Application Methods: 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).

$262
3 nmol
300 µl
SignalSilence® FoxO1 siRNA I (Mouse Specific) from Cell Signaling Technology (CST) allows the researcher to specifically inhibit FoxO1 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
Mouse

Background: The Forkhead family of transcription factors is involved in tumorigenesis of rhabdomyosarcoma and acute leukemias (1-3). Within the family, three members (FoxO1, FoxO4, and FoxO3a) have sequence similarity to the nematode orthologue DAF-16, which mediates signaling via a pathway involving IGFR1, PI3K, and Akt (4-6). Active forkhead members act as tumor suppressors by promoting cell cycle arrest and apoptosis. Increased expression of any FoxO member results in the activation of the cell cycle inhibitor p27 Kip1. Forkhead transcription factors also play a part in TGF-β-mediated upregulation of p21 Cip1, a process negatively regulated through PI3K (7). Increased proliferation results when forkhead transcription factors are inactivated through phosphorylation by Akt at Thr24, Ser256, and Ser319, which results in nuclear export and inhibition of transcription factor activity (8). Forkhead transcription factors can also be inhibited by the deacetylase sirtuin (SirT1) (9).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: CUB domain containing protein 1 (CDCP1, SIMA135) is a putative stem cell marker shown in research studies to be highly expressed in some human cancer cells and in both typical and atypical (cancerous) colons (1). Expression of CDCP1 may be epigenetically regulated, as methylation of promoter CpG sequences results in decreased CDCP1 expression (2). The corresponding CDCP1 gene encodes a glycoprotein that acts as a complex, multidomain transmembrane antigen. CDCP1 has three extracellular CUB domains that may be involved in cell adhesion or extracellular matrix interactions (1,3). Src-family kinases may phosphorylate CDCP1 at five tyrosine residues within its cytoplasmic domain to provide a potential binding site for SH2 domain-containing proteins (3). CDCP1 is a putative hematopoietic stem cell marker (4,5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

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

Background: The transcription factor proline, glutamic acid, and leucine rich protein 1 (PELP1, MNAR) mediates cell signaling through direct interaction with hormone nuclear receptors to regulate target gene transcription. This versatile protein also regulates gene expression by participating in chromatin remodeling, and acts as a cytoplasmic scaffold protein to mediate growth factor and hormone signaling (1). Following its original description as an estrogen receptor α (ERα) coactivator (2), additional research showed that PELP1 corepresses multiple nuclear hormone receptors and transcriptional regulators, including progesterone receptor, glucocorticoid receptor, AP1, and Stat3 (3). PELP1 also acts cooperatively with the secondary coactivator CARM1 at ERα target gene promoters to increase ERα-mediated transactivation (4). The PELP1 protein contains several leucine-rich repeats, important for interaction with nuclear receptors, and a carboxy-terminal glutamic acid-rich domain responsible for histone protein interaction (2). The glutamic acid-rich region of PELP1 binds to hypoacetylated histones H3 and H4 to block interaction between histone proteins and acetyltransferases. This interaction maintains histones in a hypoacetylated state and suppresses serum-response gene activation. Interaction between PELP1 and ERα relieves this repression and promotes acetylation of histone proteins (3).Research studies demonstrate altered regulation of PELP1 in several distinct hormone-dependent cancers, such as ovarian, breast, and prostate cancers (5-7). As a result, PELP1 may be a promising prognostic marker for hormone-dependent cancers, and inhibiting PELP1 expression or activity may prove beneficial in disrupting hormonal cancer initiation, progression, and metastasis (8).

$348
100 µl
This Cell Signaling Technology antibody is conjugated to biotin under optimal conditions. The biotinylated antibody is expected to exhibit the same species cross-reactivity as the unconjugated Smad1 (D59D7) XP® Rabbit mAb #6944.
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse

Application Methods: Western Blotting

Background: Bone morphogenetic proteins (BMPs) constitute a large family of signaling molecules that regulate a wide range of critical processes including morphogenesis, cell-fate determination, proliferation, differentiation, and apoptosis (1,2). BMP receptors are members of the TGF-β family of Ser/Thr kinase receptors. Ligand binding induces multimerization, autophosphorylation, and activation of these receptors (3-5). They subsequently phosphorylate Smad1 at Ser463 and Ser465 in the carboxy-terminal motif SSXS, as well as Smad5 and Smad9 (Smad8) at their corresponding sites. These phosphorylated Smads dimerize with the coactivating Smad4 and translocate to the nucleus, where they stimulate transcription of target genes (5).MAP kinases and CDKs 8 and 9 phosphorylate residues in the linker region of Smad1, including Ser206. The phosphorylation of Ser206 recruits Smurf1 to the linker region and leads to the degradation of Smad1 (6). Phosphorylation of this site also promotes Smad1 transcriptional action by recruiting YAP to the linker region (7).

$305
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to phycoerythrin (PE) 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 Cas9 (S. pyogenes) (D8Y4K) Rabbit mAb #65832.
APPLICATIONS
REACTIVITY
All Species Expected

Application Methods: Flow Cytometry

Background: The CRISPR associated protein 9 (Cas9) is an RNA-guided DNA nuclease and part of the Streptococcus pyogenes CRISPR antiviral immunity system that provides adaptive immunity against extra chromosomal genetic material (1). The CRISPR antiviral mechanism of action involves three steps: (i), acquisition of foreign DNA by host bacterium; (ii), synthesis and maturation of CRISPR RNA (crRNA) followed by the formation of RNA-Cas nuclease protein complexes; and (iii), target interference through recognition of foreign DNA by the complex and its cleavage by Cas nuclease activity (2). The type II CRISPR/Cas antiviral immunity system provides a powerful tool for precise genome editing and has potential for specific gene regulation and therapeutic applications (3). The Cas9 protein and a guide RNA consisting of a fusion between a crRNA and a trans-activating crRNA (tracrRNA) must be introduced or expressed in a cell. A 20-nucleotide sequence at the 5' end of the guide RNA directs Cas9 to a specific DNA target site. As a result, Cas9 can be "programmed" to cut various DNA sites both in vitro and in cells and organisms. CRISPR/Cas9 genome editing tools have been used in many organisms, including mouse and human cells (4,5). Research studies demonstrate that CRISPR can be used to generate mutant alleles or reporter genes in rodents and primate embryonic stem cells (6-8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Amyloid β (Aβ) precursor protein (APP) is a 100-140 kDa transmembrane glycoprotein that exists as several isoforms (1). The amino acid sequence of APP contains the amyloid domain, which can be released by a two-step proteolytic cleavage (1). The extracellular deposition and accumulation of the released Aβ fragments form the main components of amyloid plaques in Alzheimer's disease (1). APP can be phosphorylated at several sites, which may affect the proteolytic processing and secretion of this protein (2-5). Phosphorylation at Thr668 (a position corresponding to the APP695 isoform) by cyclin-dependent kinase is cell-cycle dependent and peaks during G2/M phase (4). APP phosphorylated at Thr668 exists in adult rat brain and correlates with cultured neuronal differentiation (5,6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: CENP-A is an essential histone H3 variant that replaces canonical histone H3 in centromeric heterochromatin. The inherited localization of the centromere is specified by CENP-A (1). CENP-A deposition to the correct chromosomal location in early G1 phase is regulated by the Mis18 complex, which recruits the CENP-A assembly factor/chaperone protein HJURP (Holliday Junction Recognition Protein) (2-3).Dimerization of HJURP is required for its activity (4), and phosphorylation by cyclin dependent kinases is required for temporal regulation of HJURP recruitment (5).Overexpression of HJURP causes chromosome loss in yeast and mitotic defects in mammalian cells (6). Further, downregulation of HJURP expression has been associated with replicative senescence in human cells (7).Research studies indicate that HJURP may have prognostic value in human breast cancer and high grade gliomas (8-10).

$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. The antibody is expected to exhibit the same species cross-reactivity as the unconjugated GATA-3 (D13C9) XP® Rabbit mAb #5852.
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Flow Cytometry

Background: GATA proteins comprise a group of transcription factors that are related by the presence of conserved zinc finger DNA binding domains, which bind directly to the nucleotide sequence core element GATA (1-3). There are six vertebrate GATA proteins, designated GATA-1 to GATA-6 (3).

$262
3 nmol
300 µl
SignalSilence® Stat6 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit Stat6 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: Upon activation by Janus kinases, Stat6 translocates to the nucleus where it regulates cytokine-induced gene expression. Stat6 is activated via phosphorylation at Tyr641 and is required for responsiveness to IL-4 and IL-13 (1-4). In addition, Stat6 is activated by IFN-α in B cells, where it forms transcriptionally active complexes with Stat2 and p48 (5,6). Protein phosphatase 2A is also involved in regulation of IL-4-mediated Stat6 signaling (7).