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Product listing: SignalSilence® USP10 siRNA I, UniProt ID Q14694 #7747 to SignalSilence® MTAP siRNA II, UniProt ID Q13126 #6285

$262
3 nmol
300 µl
SignalSilence® USP10 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit USP10 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: Ubiquitinating enzymes (UBEs) catalyze protein ubiquitination, a reversible process countered by deubiquitinating enzyme (DUB) action (1,2). Five DUB subfamilies are recognized, including the USP, UCH, OTU, MJD, and JAMM enzymes. USP10 possesses amino acid sequences that match the consensus cysteine and histidine boxes representative of the USP family of deubiquitinating enzymes. At the posttranslational level, USP10 appears to be regulated through both protein-protein interactions and phosphorylation. Indeed, interaction of USP10 with Ras-GAP SH3 domain binding protein (G3BP) has been found to inhibit its ability to catalyze the disassembly of ubiquitin chains (3). Furthermore, ATM-mediated phosphorylation of USP10 at Thr42 and Ser337 was shown to promote USP10 stabilization and redistribution from the cytoplasm to the nucleus, where it functions in p53 deubiquitination, stabilization, and activation in response to genotoxic stress (4). Recently, it was shown that USP10 works in concert with USP13 and Vps34 complexes. USP10, along with USP13, appears to deubiquitinate Vps34 complexes to regulate the levels of this class III PI3K. Beclin-1, another component of these complexes, functions to regulate the stability of USP13, which can deubiquitinate and stabilize the levels of USP10. Therefore, Beclin-1, can indirectly regulate p53 stability by controlling the DUB activity of USP10 (5). USP10 also functions in the endosomal compartment, where it has been shown to deubiquitinate CFTR in order to enhance its endocytic recycling and cell surface expression (6,7).

$262
3 nmol
300 µl
SignalSilence® USP1 siRNA II from Cell Signaling Technology (CST) allows the researcher to specifically inhibit USP1 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: Ubiquitinating enzymes (UBEs) catalyze protein ubiquitination, a reversible process countered by deubiquitinating enzymes (DUB) action (1,2). There are five DUB subfamilies including the USP, UCH, OTU, MJD, and JAMM enzymes. USP1 belongs to the USP subfamily and is regulated in a cell cycle dependent manner by both transcriptional and ubiquitin-proteosomal mechanisms (3). USP1 is a nuclear protein and localizes to chromatin where it is specifically associated with FANCD2. USP1 deubiquitinates monoubiquitinated FANCD2, which plays an important role in DNA damage repair and Chk1 protein stability (3,4). Another important target of USP1 is PCNA. USP1 deubiquitinates monoubiquitinated PCNA, thereby negatively regulating PCNA-mediated translesion synthesis (TLS) during DNA repair (5). USP1 interaction with UAF1, a WD40 repeat-containing protein, leads to formation of an activated USP1/UAF1 complex, which is required for the deubiquitinase activity of USP1 (6,7).

$262
3 nmol
300 µl
SignalSilence® Tyk2 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit Tyk2 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: Tyk2 is a member of the Jak family of protein tyrosine kinases. It associates with and is activated by receptors for many cytokines including IL-13, the IL-6 family, IL-10, and IFN-α and β (1-3). Following ligand binding, Tyk2 is activated by phosphorylation of Tyr1054 and/or Tyr1055 (4). Tyk2 is required for the tyrosine phosphorylation of Stat3 in the IFN-β signaling cascade (5).

$262
3 nmol
300 µl
SignalSilence® Toll-like Receptor 3 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit Toll-like Receptor 3 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: 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.

$262
3 nmol
300 µl
SignalSilence® TNF-R1 siRNA I (Mouse Specific) from Cell Signaling Technology (CST) allows the researcher to specifically inhibit TNF-R1 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: TNF-α is an important cytokine produced by numerous cell types including neutrophils, activated lymphoctyes, macrophages and NK cells. It plays a critical role in inflammatory responses and in apoptosis (1). TNF-α exists as a membrane-anchored and soluble form, both of which show biological activity. Response to TNF-α is mediated through two receptors, TNF-R1, which is widely expressed, and TNF-R2, which is expressed mainly in immune and endothelial cells (2). Antagonists to TNF-α have been validated as therapeutic targets for rheumatoid arthritis and other immune disorders (3).

$262
3 nmol
300 µl
SignalSilence® Stat5 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit Stat5 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: Stat5 is activated in response to a wide variety of ligands including IL-2, GM-CSF, growth hormone and prolactin. Phosphorylation at Tyr694 is obligatory for Stat5 activation (1,2). This phosphorylation is mediated by Src upon erythropoietin stimulation (3). Stat5 is constitutively active in some leukemic cell types (4). Phosphorylated Stat5 is found in some endothelial cells treated with IL-3, which suggests its involvement in angiogenesis and cell motility (5). Stat5a and Stat5b are independently regulated and activated in various cell types. For instance, interferon treatment predominantly activates Stat5a in U-937 cells and Stat5b in HeLa cells (6).

$262
3 nmol
300 µl
SignalSilence® Smad1 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit Smad1 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: 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).

$262
3 nmol
300 µl
SignalSilence® Sharpin siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit sharpin 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: SHank-Associated RH domain-interacting ProteIN (Sharpin), also known as SIPL1, is a highly conserved gene among many mammalian species and is ubiquitously expressed in various types of cells and tissues. Sharpin harbors multiple functional motifs including an amino terminal coiled-coil (CC) domain, which has been shown to mediate the interaction between sharpin and the scaffold protein shank (1). The other two domains, ubiquitin-like domain (UBL) and NPL4 zinc finger domain (NZF), facilitate ubiquitin-mediated protein recognition and degradation (2). Recent studies have shown that both UBL and NZF domains are essential for sharpin to exert its function in part through ubiquitin-mediated mechanisms (3-5). Although sharpin was initially identified as a scaffold protein within the postsynaptic density of neurons (1), recent studies have identified sharpin as a novel modulator of immune and inflammatory diseases. An emerging mechanistic model suggests that sharpin functions as an important adaptor component of the linear ubiquitin chain assembly complex (LUBAC) that modulates activation of the canonical NF-κB signaling pathway (3,4,6,7), thereby regulating cell survival and apoptosis, cytokine production, and development of lymphoid tissues. Indeed, mice with spontaneous mutations in the Sharpin gene develop chronic proliferative dermatitis that is characterized by eosinophilic inflammation of the skin and dysregulated development of lymphoid tissues (8).

$262
3 nmol
300 µl
SignalSilence® SET8 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit SET8 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 protein expression by western analysis.
REACTIVITY
Human

Background: SET domain-containing lysine methyltransferase 8 (SET8), also known as PR/SET domain-containing protein 7 (PR/SET7), is a member of a family of histone lysine methyltransferases, each of which contains a conserved catalytic SET domain originally identified in Drosophila Su[var]3-9, Enhancer of zeste, and Trithorax proteins (1-3). SET8 is a single-subunit enzyme that mono-methylates histone H4 on Lys20, preferably on nucleosomal substrates (1-3). SET8 protein levels and Histone H4 Lys20 methylation are cell cycle regulated, both increasing in S phase and peaking at G2/M phase (4,5). SET8 interacts with the PCNA protein, associates with sites of active DNA synthesis, and is required for DNA replication and genome stability during S phase (5-7). Inhibition of SET8 using shRNA or siRNA results in arrest of replication forks, induction of double-stranded DNA breaks, and a Chk1-mediated cell-cycle arrest in S and G2/M phases of the cell cycle (6,7). Furthermore, SET8 methylates p53 on Lys382, down regulating the pro-apoptotic and checkpoint activation functions of p53 (8). In response to DNA damage, SET8 expression levels decrease, allowing p53 to activate checkpoints and/or apoptosis (8). Both the methylation of histone H4 Lys20 and p53 appear to be important for the functions of SET8 in S phase.

$262
3 nmol
300 µl
SignalSilence® RSK1 siRNA II from Cell Signaling Technology (CST) allows the researcher to specifically inhibit RSK1 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 protein expression by western analysis.
REACTIVITY
Human

Background: The 90 kDa ribosomal S6 kinases (RSK1-4) are a family of widely expressed Ser/Thr kinases characterized by two nonidentical, functional kinase domains (1) and a carboxy-terminal docking site for extracellular signal-regulated kinases (ERKs) (2). Several sites both within and outside of the RSK kinase domain, including Ser380, Thr359, Ser363, and Thr573, are important for kinase activation (3). RSK1-3 are activated via coordinated phosphorylation by MAPKs, autophosphorylation, and phosphoinositide-3-OH kinase (PI3K) in response to many growth factors, polypeptide hormones, and neurotransmitters (3).

$262
3 nmol
300 µl
SignalSilence® RKIP siRNA II from Cell Signaling Technology (CST) allows the researcher to specifically inhibit RKIP 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: Raf kinase inhibitor protein (RKIP) is a member of the phosphatidylethanolamine-binding protein (PEBP) family that associates with Raf-1 and the MEK and MAP kinases (1). RKIP has been shown to form a complex with Raf-1, MEK, and Erk (2). Although MEK and Erk can simultaneously bind RKIP, the association between Raf-1 and RKIP and that of RKIP and MEK are mutually exclusive. Thus, RKIP competitively disrupts the Raf-1-MEK complex and effectively terminates signal transmission from Raf-1 to MAP kinases (2). The inhibitory effect of RKIP on MAP kinase signaling is eliminated by PKC phosphorylation of RKIP at Ser153 (3). PKC phosphorylation on Ser153 also promotes the association of RKIP with GRK2, which prevents GRK2-dependent internalization of GPCR (4). RKIP also interacts with modules of the NF-κB pathway, including NF-κB-inducing kinase (NIK), TAK1, IKKα and IKKβ (5). These interactions antagonize cytokine-induced activation of the NF-κB pathway (5). Restoration of RKIP expression is associated with the inhibition of prostate cancer metastasis, implying that RKIP may be a potential clinical target as a suppressor of tumor metastasis through inhibition of vascular invasion (6).

$262
3 nmol
300 µl
SignalSilence® Rb siRNA II from Cell Signaling Technology (CST) allows the researcher to specifically inhibit Rb 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 retinoblastoma tumor suppressor protein Rb regulates cell proliferation by controlling progression through the restriction point within the G1-phase of the cell cycle (1). Rb has three functionally distinct binding domains and interacts with critical regulatory proteins including the E2F family of transcription factors, c-Abl tyrosine kinase, and proteins with a conserved LXCXE motif (2-4). Cell cycle-dependent phosphorylation by a CDK inhibits Rb target binding and allows cell cycle progression (5). Rb inactivation and subsequent cell cycle progression likely requires an initial phosphorylation by cyclin D-CDK4/6 followed by cyclin E-CDK2 phosphorylation (6). Specificity of different CDK/cyclin complexes has been observed in vitro (6-8) and cyclin D1 is required for Ser780 phosphorylation in vivo (9).

$262
3 nmol
300 µl
SignalSilence® PTP1B siRNA II from Cell Signaling Technology (CST) allows the researcher to specifically inhibit PTP1B 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: Protein-tyrosine phosphatase 1B (PTP1B) is the original member of the protein tyrosine phosphatase (PTP) family of proteins (1). PTP1B is highly expressed in insulin-responsive tissues and negatively regulates insulin, as well as integrin, through dephosphorylation of phosphotyrosine residues (2-4). PTP1B knockout mice show resistance to dietary weight gain and enhanced insulin sensitivity, suggesting a possible role in treatment of obesity as well as type 2 diabetes (5).

$262
3 nmol
300 µl
SignalSilence® PTP1B siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit PTP1B 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: Protein-tyrosine phosphatase 1B (PTP1B) is the original member of the protein tyrosine phosphatase (PTP) family of proteins (1). PTP1B is highly expressed in insulin-responsive tissues and negatively regulates insulin, as well as integrin, through dephosphorylation of phosphotyrosine residues (2-4). PTP1B knockout mice show resistance to dietary weight gain and enhanced insulin sensitivity, suggesting a possible role in treatment of obesity as well as type 2 diabetes (5).

$262
3 nmol
300 µl
SignalSilence® PKCζ siRNA II from Cell Signaling Technology (CST) allows the researcher to specifically inhibit PKCζ expression by 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: Activation of protein kinase C (PKC) is one of the earliest events in a cascade that controls a variety of cellular responses, including secretion, gene expression, proliferation, and muscle contraction (1,2). PKC isoforms belong to three groups based on calcium dependency and activators. Classical PKCs are calcium-dependent via their C2 domains and are activated by phosphatidylserine (PS), diacylglycerol (DAG), and phorbol esters (TPA, PMA) through their cysteine-rich C1 domains. Both novel and atypical PKCs are calcium-independent, but only novel PKCs are activated by PS, DAG, and phorbol esters (3-5). Members of these three PKC groups contain a pseudo-substrate or autoinhibitory domain that binds to substrate-binding sites in the catalytic domain to prevent activation in the absence of cofactors or activators. Control of PKC activity is regulated through three distinct phosphorylation events. Phosphorylation occurs in vivo at Thr500 in the activation loop, at Thr641 through autophosphorylation, and at the carboxy-terminal hydrophobic site Ser660 (2). Atypical PKC isoforms lack hydrophobic region phosphorylation, which correlates with the presence of glutamic acid rather than the serine or threonine residues found in more typical PKC isoforms. The enzyme PDK1 or a close relative is responsible for PKC activation. A recent addition to the PKC superfamily is PKCμ (PKD), which is regulated by DAG and TPA through its C1 domain. PKD is distinguished by the presence of a PH domain and by its unique substrate recognition and Golgi localization (6). PKC-related kinases (PRK) lack the C1 domain and do not respond to DAG or phorbol esters. Phosphatidylinositol lipids activate PRKs, and small Rho-family GTPases bind to the homology region 1 (HR1) to regulate PRK kinase activity (7).

$262
3 nmol
300 µl
SignalSilence® PKCα siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit PKCα 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: Activation of protein kinase C (PKC) is one of the earliest events in a cascade that controls a variety of cellular responses, including secretion, gene expression, proliferation, and muscle contraction (1,2). PKC isoforms belong to three groups based on calcium dependency and activators. Classical PKCs are calcium-dependent via their C2 domains and are activated by phosphatidylserine (PS), diacylglycerol (DAG), and phorbol esters (TPA, PMA) through their cysteine-rich C1 domains. Both novel and atypical PKCs are calcium-independent, but only novel PKCs are activated by PS, DAG, and phorbol esters (3-5). Members of these three PKC groups contain a pseudo-substrate or autoinhibitory domain that binds to substrate-binding sites in the catalytic domain to prevent activation in the absence of cofactors or activators. Control of PKC activity is regulated through three distinct phosphorylation events. Phosphorylation occurs in vivo at Thr500 in the activation loop, at Thr641 through autophosphorylation, and at the carboxy-terminal hydrophobic site Ser660 (2). Atypical PKC isoforms lack hydrophobic region phosphorylation, which correlates with the presence of glutamic acid rather than the serine or threonine residues found in more typical PKC isoforms. The enzyme PDK1 or a close relative is responsible for PKC activation. A recent addition to the PKC superfamily is PKCμ (PKD), which is regulated by DAG and TPA through its C1 domain. PKD is distinguished by the presence of a PH domain and by its unique substrate recognition and Golgi localization (6). PKC-related kinases (PRK) lack the C1 domain and do not respond to DAG or phorbol esters. Phosphatidylinositol lipids activate PRKs, and small Rho-family GTPases bind to the homology region 1 (HR1) to regulate PRK kinase activity (7).

$262
3 nmol
300 µl
SignalSilence® PEA-15 siRNA II from Cell Signaling Technology (CST) allows the researcher to specifically inhibit PEA-15 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: PEA-15 is a 15 kDa phosphoprotein expressed abundantly in astrocytes and fibroblasts as well as in tissues, including the lung and eye (1). The protein has been shown to coordinate cell growth, death, and glucose utilization (2-4). The amino-terminal DED domain of PEA-15 mediates its binding to FADD or Erk and further regulates the Erk and apoptosis signaling pathways. PEA-15 can be phosphorylated at two serine residues, Ser104 and Ser116, located within the carboxy terminus. Phosphorylation at these sites regulates binding to Erk and FADD (2,3).

$262
3 nmol
300 µl
SignalSilence® PARP siRNA II (Mouse Specific) from Cell Signaling Technology (CST) allows the researcher to specifically inhibit PARP 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: PARP, a 116 kDa nuclear poly (ADP-ribose) polymerase, appears to be involved in DNA repair in response to environmental stress (1). This protein can be cleaved by many ICE-like caspases in vitro (2,3) and is one of the main cleavage targets of caspase-3 in vivo (4,5). In human PARP, the cleavage occurs between Asp214 and Gly215, which separates the PARP amino-terminal DNA binding domain (24 kDa) from the carboxy-terminal catalytic domain (89 kDa) (2,4). PARP helps cells to maintain their viability; cleavage of PARP facilitates cellular disassembly and serves as a marker of cells undergoing apoptosis (6).

$262
3 nmol
300 µl
SignalSilence® PARP siRNA I (Mouse Specific) from Cell Signaling Technology (CST) allows the researcher to specifically inhibit PARP 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: PARP, a 116 kDa nuclear poly (ADP-ribose) polymerase, appears to be involved in DNA repair in response to environmental stress (1). This protein can be cleaved by many ICE-like caspases in vitro (2,3) and is one of the main cleavage targets of caspase-3 in vivo (4,5). In human PARP, the cleavage occurs between Asp214 and Gly215, which separates the PARP amino-terminal DNA binding domain (24 kDa) from the carboxy-terminal catalytic domain (89 kDa) (2,4). PARP helps cells to maintain their viability; cleavage of PARP facilitates cellular disassembly and serves as a marker of cells undergoing apoptosis (6).

$262
3 nmol
300 µl
SignalSilence® PAK1 siRNA I (Mouse Specific) from Cell Signaling Technology (CST) allows the researcher to specifically inhibit PAK1 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 p21-activated kinase (PAK) family of serine/threonine kinases is engaged in multiple cellular processes, including cytoskeletal reorganization, MAPK signaling, apoptotic signaling, control of phagocyte NADPH oxidase, and growth factor-induced neurite outgrowth (1,2). Several mechanisms that induce PAK activity have been reported. Binding of Rac/Cdc42 to the CRIB (or PBD) domain near the amino terminus of PAK causes autophosphorylation and conformational changes in PAK (1). Phosphorylation of PAK1 at Thr423 by PDK induces activation of PAK1 (3). Several autophosphorylation sites have been identified, including Ser199 and Ser204 of PAK1 and Ser192 and Ser197 of PAK2 (4,5). Because the autophosphorylation sites are located in the amino-terminal inhibitory domain, it has been hypothesized that modification in this region prevents the kinase from reverting to an inactive conformation (6). Research indicates that phosphorylation at Ser144 of PAK1 or Ser139 of PAK3 (located in the kinase inhibitory domain) affects kinase activity (7). Phosphorylation at Ser21 of PAK1 or Ser20 of PAK2 regulates binding with the adaptor protein Nck (8). PAK4, PAK5, and PAK6 have lower sequence similarity with PAK1-3 in the amino-terminal regulatory region (9). Phosphorylation at Ser474 of PAK4, a site analogous to Thr423 of PAK1, may play a pivotal role in regulating the activity and function of PAK4 (10).

$262
3 nmol
300 µl
SignalSilence® PAK1 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit PAK1 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: The p21-activated kinase (PAK) family of serine/threonine kinases is engaged in multiple cellular processes, including cytoskeletal reorganization, MAPK signaling, apoptotic signaling, control of phagocyte NADPH oxidase, and growth factor-induced neurite outgrowth (1,2). Several mechanisms that induce PAK activity have been reported. Binding of Rac/Cdc42 to the CRIB (or PBD) domain near the amino terminus of PAK causes autophosphorylation and conformational changes in PAK (1). Phosphorylation of PAK1 at Thr423 by PDK induces activation of PAK1 (3). Several autophosphorylation sites have been identified, including Ser199 and Ser204 of PAK1 and Ser192 and Ser197 of PAK2 (4,5). Because the autophosphorylation sites are located in the amino-terminal inhibitory domain, it has been hypothesized that modification in this region prevents the kinase from reverting to an inactive conformation (6). Research indicates that phosphorylation at Ser144 of PAK1 or Ser139 of PAK3 (located in the kinase inhibitory domain) affects kinase activity (7). Phosphorylation at Ser21 of PAK1 or Ser20 of PAK2 regulates binding with the adaptor protein Nck (8). PAK4, PAK5, and PAK6 have lower sequence similarity with PAK1-3 in the amino-terminal regulatory region (9). Phosphorylation at Ser474 of PAK4, a site analogous to Thr423 of PAK1, may play a pivotal role in regulating the activity and function of PAK4 (10).

$262
3 nmol
300 µl
SignalSilence® p70/85 S6 Kinase siRNA II from Cell Signaling Technology (CST) allows the researcher to specifically inhibit p70/85 S6 kinase 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: p70 S6 kinase is a mitogen activated Ser/Thr protein kinase that is required for cell growth and G1 cell cycle progression (1,2). p70 S6 kinase phosphorylates the S6 protein of the 40S ribosomal subunit and is involved in translational control of 5' oligopyrimidine tract mRNAs (1). A second isoform, p85 S6 kinase, is derived from the same gene and is identical to p70 S6 kinase except for 23 extra residues at the amino terminus, which encode a nuclear localizing signal (1). Both isoforms lie on a mitogen activated signaling pathway downstream of phosphoinositide-3 kinase (PI-3K) and the target of rapamycin, FRAP/mTOR, a pathway distinct from the Ras/MAP kinase cascade (1). The activity of p70 S6 kinase is controlled by multiple phosphorylation events located within the catalytic, linker and pseudosubstrate domains (1). Phosphorylation of Thr229 in the catalytic domain and Thr389 in the linker domain are most critical for kinase function (1). Phosphorylation of Thr389, however, most closely correlates with p70 kinase activity in vivo (3). Prior phosphorylation of Thr389 is required for the action of phosphoinositide 3-dependent protein kinase 1 (PDK1) on Thr229 (4,5). Phosphorylation of this site is stimulated by growth factors such as insulin, EGF and FGF, as well as by serum and some G-protein-coupled receptor ligands, and is blocked by wortmannin, LY294002 (PI-3K inhibitor) and rapamycin (FRAP/mTOR inhibitor) (1,6,7). Ser411, Thr421 and Ser424 lie within a Ser-Pro-rich region located in the pseudosubstrate region (1). Phosphorylation at these sites is thought to activate p70 S6 kinase via relief of pseudosubstrate suppression (1,2). Another LY294002 and rapamycin sensitive phosphorylation site, Ser371, is an in vitro substrate for mTOR and correlates well with the activity of a partially rapamycin resistant mutant p70 S6 kinase (8).

$262
3 nmol
300 µl
SignalSilence® p38γ MAPK siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit p38γ MAPK 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: 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).

$262
3 nmol
300 µl
SignalSilence® p38β MAPK siRNA II from Cell Signaling Technology (CST) allows the researcher to specifically inhibit p38β MAPK 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: 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).

$262
3 nmol
300 µl
SignalSilence® p38β MAPK siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit p38β MAPK 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: 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).

$262
3 nmol
300 µl
SignalSilence® p38α MAPK siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit p38α MAPK 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: 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).

$262
3 nmol
300 µl
SignalSilence® OTULIN siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit OTULIN 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: Protein ubiquitination and deubiquitination are reversible processes catalyzed by ubiquitinating enzymes (UBEs) and deubiquitinating enzymes (DUBs) (1,2). Five subfamilies of DUBs have been characterized to date, and include USP, UCH, OTU, MJD, and JAMM deubiquitinating enzymes (1,2). The ovarian tumor (OTU) DUB subfamily comprises a group of approximately 100 putative cysteine proteases that are homologous to the Drosophila ovarian tumor gene product (3). OTU domain-containing deubiquitinase with linear linkage specificity (OTULIN, FAM105B, Gumby) is an OTU subfamily deubiquitinating enzyme that antagonizes the E3 linear ubiquitin chain assembly complex (LUBAC) by promoting disassembly of Met1-linked (linear) ubiquitin chains (4,5). LUBAC and OTULIN regulate NOD2 signaling in an antagonistic manner by controlling the level of Met1-ubiquitinated RIPK2 kinase (6). Binding of the OTULIN PUB-interacting motif to the HOIP subunit of LUBAC is critical for OTULIN inhibition of NF-κΒ signaling; this OTULIN-HOIP interaction is negatively regulated by tyrosine phosphorylation of OTULIN (7,8). The ability of OTULIN to influence LUBAC function and the presence of linear ubiquitin chains may play an important role in regulating angiogenesis, craniofacial, and neural development (5).

$262
3 nmol
300 µl
SignalSilence® OSR1 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit OSR1 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: SPAK (STE20/SPS1-related Pro/Ala-rich kinase) and OSR1 (oxidative stress responsive 1) are members of the GCK family serine/threonine kinases. Overexpression and in vitro studies demonstrate that SPAK is able to activate p38 MAP kinase indicating a possible role for SPAK in the stress response (1). Yeast two-hybrid screening revealed that SPAK and OSR1 bind to Na-K-2Cl cotransporters NKCC1 and NKCC2 and K-Cl cotransporter KCC3 (2). WNK1 and WNK4 phosphorylate SPAK at Thr243/247 and Ser380 (3-5). Similarly, WNK1 and WNK4 phosphorylate OSR1 at Thr185 and Ser315 (3,4). Phosphorylation at these sites stimulates SPAK and OSR1 activity, leading to NKCC1 phosphorylation and enhanced NKCC1 activity (3-5). SPAK is also phosphorylated at Ser311 by PKCθ in response to T cell activation. Substitution of Ser311 with Ala or specific siRNA knock-down of SPAK dramatically reduces TCR/CD28-induced AP-1 activation, suggesting SPAK is involved in T cell signaling as well (6).

$262
3 nmol
300 µl
SignalSilence® mTOR siRNA II (Mouse Specific) from Cell Signaling Technology (CST) allows the researcher to specifically inhibit mTOR 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 mammalian target of rapamycin (mTOR, FRAP, RAFT) is a Ser/Thr protein kinase (1-3) that functions as an ATP and amino acid sensor to balance nutrient availability and cell growth (4,5). When sufficient nutrients are available, mTOR responds to a phosphatidic acid-mediated signal to transmit a positive signal to p70 S6 kinase and participate in the inactivation of the eIF4E inhibitor, 4E-BP1 (6). These events result in the translation of specific mRNA subpopulations. mTOR is phosphorylated at Ser2448 via the PI3 kinase/Akt signaling pathway and autophosphorylated at Ser2481 (7,8). mTOR plays a key role in cell growth and homeostasis and may be abnormally regulated in tumors. For these reasons, mTOR is currently under investigation as a potential target for anti-cancer therapy (9).

$262
3 nmol
300 µl
SignalSilence® MTAP siRNA II from Cell Signaling Technology (CST) allows the researcher to specifically inhibit MTAP 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: MTAP is an enzyme that is essential for the salvage pathway for both adenine and methionine synthesis. MTAP catalyzes the cleavage of 5’-methylthioadenosine into adenine and 5-methylthio-D-ribose-1-phosphate. Adenine is then used to generate AMP whereas 5-methylthio-D-ribose-1-phosphate is converted into methionine (1,2). MTAP is expressed in all normal cells and tissues, although frequently lost in different human tumors including pancreatic adenocarcinoma, neuroendocrine tumors, non-small cell lung carcinoma and breast carcinoma. MTAP is usually codeleted with p16 (cdkN2a/ARF) (3-5). MTAP overexpression in breast cancer cells inhibits their ability to form colonies in soft agar, thereby implicating its function as a tumor suppressor (6).