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Product listing: Paip2A Antibody, UniProt ID Q9BPZ3 #4422 to Mic-1 (Y60) Antibody, UniProt ID Q99988 #3249

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

Application Methods: Western Blotting

Background: The eukaryotic mRNA 3' poly(A) tail interacts with the 5' cap structure to regulate translation of mRNA transcripts (1). The eIF4G translation initiation factor associates with poly(A) binding protein (PABP) to circularize mRNA (1,2). Paip1 is a PABP interacting protein that binds eIF4A to stimulate translation (3). A second PABP binding protein, Paip2, inhibits translation by interfering with PABP function. Specifically, Paip2 reduces the affinity of PABP for poly(A) RNA and competes with Paip1 for PABP binding (1,2).

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

Application Methods: Western Blotting

Background: Twinfilin is an actin monomer-binding protein found in all eukaryotes (1). Mammals have three isoforms. Twinfilin-1 and twinfilin-2a are expressed in most non-muscle cell types, whereas twinfilin-2b is the main isoform in adult heart and skeletal muscle (2). Twinfilins are composed of two ADF-homology domains connected by a 30 kDa linker region. All twinfilins have been shown to form a 1:1 complex with G-actin, but not F-actin (reviewed in 3). Twinfilin-1 was originally known as A6 protein tyrosine kinase and thought to be part of a novel class of protein kinases. However, the protein was renamed after further studies showed no evidence of tyrosine kinase activity (4). Twinfilin-1 helps to prevent the actin filament assembly by forming a complex with actin monomers and, in mammals, has been shown to cap the filament barbed ends. It has been suggested that this regulates cell motility (5). Suppression of twinfilin-1 has also been shown to slow lymphoma cell migration to lymph nodes (6).

$263
100 tests
500 µl
This Cell Signaling Technology antibody is conjugated to violetFluor™ 450 and tested in-house for direct flow cytometry analysis in human cells.
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry

Background: Cluster of Differentiation 4 (CD4) is a glycoprotein composed of an amino-terminal extracellular domain (four domains: D1-D4 with Ig-like structures), a transmembrane part and a short cytoplasmic tail. CD4 is expressed on the surface of T helper cells, regulatory T cells, monocytes, macrophages and dendritic cells, and plays an important role in the development and activation of T cells. On T cells, CD4 is the co-receptor for the T cell receptor (TCR), and these two distinct structures recognize the Antigen–Major Histocompatibility Complex (MHC). Specifically, the D1 domain of CD4 interacts with the β2-domain of the MHC class II molecule. CD4 ensures specificity of the TCR–antigen interaction, prolongs the contact between the T cell and the antigen presenting cell and recruits the tyrosine kinase Lck, which is essential for T cell activation (1).

$263
100 tests
500 µl
This Cell Signaling Technology antibody is conjugated to PE and tested in-house for direct flow cytometry analysis in human cells.
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry

Background: CD14 is a leucine-rich repeat-containing pattern recognition receptor with expression largely restricted to the monocyte/macrophage cell lineage (1). Research studies have shown that CD14 is a bacterial lipopolysaccharide (LPS) binding glycoprotein, expressed as either a GPI-linked membrane protein or a soluble plasma protein (2). LPS induces an upregulation of GPI-linked CD14 expression, which facilitates TLR4 signaling and macrophage activation in response to bacterial infection (3-5).

$229
100 µg
This Cell Signaling Technology antibody is conjugated to APC and tested in-house for direct flow cytometric analysis in mouse cells.
APPLICATIONS
REACTIVITY
Mouse

Application Methods: Flow Cytometry

Background: F4/80 (EMR1) is a heavily glycosylated G-protein-coupled receptor and is a well-established marker for mouse macrophages (1-3). Expression of F4/80 has also been observed in microglia and subset populations of dendritic cells (4).

$262
3 nmol
300 µl
SignalSilence® Acetyl-CoA Carboxylase 1 siRNA II from Cell Signaling Technology (CST) allows the researcher to specifically inhibit Acetyl-CoA Carboxylase 1 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: Acetyl-CoA carboxylase (ACC) catalyzes the carboxylation of acetyl-CoA to malonyl-CoA (1). It is the key enzyme in the biosynthesis and oxidation of fatty acids (1). In rodents, the 265 kDa ACC1 (ACCα) form is primarily expressed in lipogenic tissues, while 280 kDa ACC2 (ACCβ) is the main isoform in oxidative tissues (1,2). However, in humans, ACC2 is the predominant isoform in both lipogenic and oxidative tissues (1,2). Phosphorylation by AMPK at Ser79 or by PKA at Ser1200 inhibits the enzymatic activity of ACC (3). ACC is a potential target of anti-obesity drugs (4,5).

$262
50-100 transfections
300 µl
SignalSilence® MEK2 siRNA from Cell Signaling Technology allows the researcher to specifically inhibit MEK2 expression using RNA interference, a method in which 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 in specified cell lines.
REACTIVITY
Human

Background: MEK1 and MEK2, also called MAPK or Erk kinases, are dual-specificity protein kinases that function in a mitogen activated protein kinase cascade controlling cell growth and differentiation (1-3). Activation of MEK1 and MEK2 occurs through phosphorylation of two serine residues at positions 217 and 221, located in the activation loop of subdomain VIII, by Raf-like molecules. MEK1/2 is activated by a wide variety of growth factors and cytokines and also by membrane depolarization and calcium influx (1-4). Constitutively active forms of MEK1/2 are sufficient for the transformation of NIH/3T3 cells or the differentiation of PC-12 cells (4). MEK activates p44 and p42 MAP kinase by phosphorylating both threonine and tyrosine residues at sites located within the activation loop of kinase subdomain VIII.

$262
3 nmol
300 µl
SignalSilence® Met siRNA II from Cell Signaling Technology (CST) allows the researcher to specifically inhibit Met 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: Met, a high affinity tyrosine kinase receptor for hepatocyte growth factor (HGF, also known as scatter factor) is a disulfide-linked heterodimer made of 45 kDa α- and 145 kDa β-subunits (1,2). The α-subunit and the amino-terminal region of the β-subunit form the extracellular domain. The remainder of the β-chain spans the plasma membrane and contains a cytoplasmic region with tyrosine kinase activity. Interaction of Met with HGF results in autophosphorylation at multiple tyrosines, which recruit several downstream signaling components, including Gab1, c-Cbl, and PI3 kinase (3). These fundamental events are important for all of the biological functions involving Met kinase activity. The addition of a phosphate at cytoplasmic Tyr1003 is essential for Met protein ubiquitination and degradation (4). Phosphorylation at Tyr1234/1235 in the Met kinase domain is critical for kinase activation. Phosphorylation at Tyr1349 in the Met cytoplasmic domain provides a direct binding site for Gab1 (5). Research studies have shown that altered Met levels and/or tyrosine kinase activities are found in several types of tumors, including renal, colon, and breast. Thus, investigators have concluded that Met is an attractive potential cancer therapeutic and diagnostic target (6,7).

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

Application Methods: Western Blotting

Background: The Mitotic Checkpoint Complex (MCC), which contains Bub1, Bub1b, Bub3, Mad2, and Cdc20, controls chromosome segregation and monitors kinetochore-microtubule interactions (1). During mitosis, the MCC complex inhibits the ubiquitin ligase activity of the Anaphase Promoting Complex/Cyclosome (APC/C), thereby preventing cells with unaligned chromosomes from prematurely entering anaphase (2). Research studies have shown that Bub1b and Bub1 kinases are mutated in several types of human malignancies including hematopoietic, colorectal, lung, and breast cancers (3). Biallelic mutations in Bub1b have been found in mosaic variegated aneuploidy syndrome and premature chromatid separation syndrome (4). Bub1b mouse germline knockouts are embryonic lethal with heterozygous animals displaying genetic instability, early aging phenotypes, and increased cancer susceptibility (5). Bub3 binds both Bub1 and Bub1b, facilitating their recruitment to kinetochores (6), and is required for functional microtubule-kinetochore interactions (7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: CD83 is a single-transmembrane protein with a calculated molecular weight (MW) of 23 kDa, but due to heavy and differential glycosylation, its apparent MW ranges from 23 to 70 kDa. CD83 is predominantly expressed on mature dendritic cells (DCs) and has been used as a DC activation/maturation marker as its increased expression is correlated with upregulation of HLA class II antigen expression on DCs (1-3). CD83 is also expressed at a low level on lymphocytes and is upregulated upon lymphocyte activation (4, 5). Thymic epithelial cells also express CD83, which is required for normal CD4+ T cell development (6, 7). CD83 is also expressed as a soluble form (sCD83) that can be found in serum of healthy adults (8). sCD83 has been shown to negatively regulate immune response by lymphocytes (9, 10).

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

Application Methods: Western Blotting

Background: The NDK/NME/NM23 kinase family (encoded by the NME gene family) consists of at least eight distinct proteins that exhibit different cellular localization (1). Members of this group inhibit metastasis in a variety of tumor cell types (2). All NDK/NME/NM23 proteins possess nucleoside diphosphatase kinase (NDK) activity and catalyze the phosphorylation of nucleoside diphosphate to the corresponding nucleoside triphosphate to regulate a diverse array of cellular events (3). At least four classes of NDK biochemical activities have been described, including protein-protein interactions (4-6), regulation of GTP-binding protein function (7-9), DNA-associated activities (10,11), and histidine-dependent protein phosphotransferase activity (12). NDK/NME proteins participate in the regulation of a broad spectrum of cellular responses, including development, differentiation, proliferation, endocytosis, and apoptosis (13). Because of its role in metastasis suppression and oncogenesis, NDKA (NME1/NM23-H1) has been widely studied (14). NDKA (NM23-H1) and NDKB (NM23-H2) are encoded by adjacent NME1 and NME2 genes and share 90% sequence identity. Two serine residues (Ser122 and Ser144) on NDKA/NM23-H1 can be phosphorylated by AMPKα1, but only phosphorylation at Ser122 determines whether NDKA channels ATP to AMPKα1. This regulates AMPKα1 activity towards ACC1, an important regulator of fatty acid metabolism (15). Mutation of NDKB/NM23-H2 at Ser122 (S122P) in melanoma cells results in altered phosphoryl transfer activity (16).

$260
100 µl
APPLICATIONS
REACTIVITY
Mouse, Rat

Application Methods: Western Blotting

Background: SynGAP is a synaptic GTPase-activating protein selectively expressed in the brain and found at higher concentrations specifically at excitatory synapses in the mammalian forebrain. SynGAP has a PH domain, a C2 domain, and a highly conserved RasGAP domain, which negatively regulates both Ras activity and its downstream signaling pathways. SynGAP interacts with the PDZ domains of SAP102, as well as PSD95, a postsynaptic scaffolding protein that couples SynGAP to NMDA receptors (1). SynGAP is phosphorylated by Ca2+/calmodulin-dependent protein kinase II (CaMKII) at Ser765 and Ser1123, among other sites (2,3). Phosphorylation of SynGAP results in stimulation of the GTPase activity of Ras, and PSD95 dependent CaMKII phosphorylation of SynGAP increases after transient brain ischemia (1,4). SynGAP is implicated in NMDAR- and CaMKII-dependent regulation of AMPAR trafficking and plays an important role in synaptic plasticity (3,5). SynGAP is critical during neuronal development as mice lacking SynGAP protein die postnatally. Furthermore, SynGAP mutant mice have reduced long-term potentiation (LTP) and perform poorly in spatial memory tasks (6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Sigma non-opioid intracellular receptor 1 (SIGMAR1) is an endoplasmic reticulum (ER) membrane chaperone that forms raft-like microdomains on the ER, where it interacts with mitochondria at the mitochondria-associated ER membrane domain (MAM). At MAM, SIGMAR1 maintains proper ER-mitochondrion Ca2+ signaling, regulates mitochondria function, and enhances cellular survival upon ER stress (1-4). When activated, SIGMAR1 translocates to ER and plasma membrane, where it interacts with a plethora of membrane proteins, including ion channels, neurotransmitter receptors, and kinases. SIGMAR1 also modulates a variety of neuronal functions, such as neuronal excitability, neuroplasticity, neuroprotection, and neurorestoration (5-7). SIGMAR1 binds to many anti-psychotic drugs and it is implicated in addiction, pain, neurodegenerative diseases, and depression (8-11). Recently, mutations in the SIGMAR1 gene have been reported to be associated with amyotrophic lateral sclerosis (12,13). Besides its important roles in central nervous system and peripheral nervous system, SIGMAR1 also enhances cancer cell migration and invasion (14,15).

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

Application Methods: Western Blotting

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).

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

Application Methods: Western Blotting

Background: WW-domain binding protein 2 (WBP2) is an adaptor protein first identified in a screen for proteins that interact with YAP1 (1). WBP2 was subsequently shown to bind other WW domain-containing proteins, including TAZ and NEDD4-like ubiquitin-protein ligases (2-5). There is strong evidence for a conserved functional role for WBP2 in the Hippo kinase tumor suppressor pathway. WBP2 interaction is required for the oncogenic properties of TAZ in breast cancer cells (4) and the growth-promoting properties of the YAP homolog Yorkie in Drosophila (6). In vitro studies have also suggested that WBP2 may act as a transcriptional co-activator of both estrogen and progesterone receptors (7); this interaction was shown to be dependent upon tyrosine phosphorylation of WBP2 by c-Src and c-Yes kinases (8).

$269
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

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

Background: MGMT (O-6-methylguanine-DNA methyltransferase) is a DNA repair enzyme that participates in a suicide reaction that specifically removes methyl or alkyl groups from the O(6) position of guanine, restoring guanine to its normal form without causing DNA breaks (1). MGMT protects cells from alkylating toxins, and is an important factor in drug resistance to alkylating therapeutic agents (2,3). It is ubiquitously expressed in normal human tissues (4) and is overexpressed in many types of human tumors, but epigenetically silenced in other tumors. MGMT silencing is a marker associated with poor prognosis, but is a good predictive marker for response to alkylating agent chemotherapy (5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: RBM10 is an RNA binding protein and a paralog to tumor suppressor RBM5 (1,2). Alternative splicing creates two highly expressed variants that differ by one exon. RBM10 controls alternative splicing and exon skipping of mRNAs, including Fas and Bcl-x (3,4). RBM10 has been shown to affect apoptosis via up regulation of TNF-α mRNA (5). In lung cancer, RBM10 mutations disrupt the splicing of NUMB, a regulator of Notch signaling (6,7). Fusion of the RBM10 gene with TFE3 has been found in renal cell carcinoma (8-9). Mutations of RBM10 causes TARP syndrome, an x-linked, lethal disorder characterized by various developmental defects (10-12).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: In mammalian cells, the significance of histone H2B ubiquitination in chromatin epigenetics came from the identification of the budding yeast protein Bre1 (1,2). Together with the ubiquitin-conjugating enzyme Rad6, Bre1 serves as the E3 ligase in the monoubiquitination of the yeast histone H2B within transcribed regions of chromatin (1-3). Subsequently, the mammalian orthologs of yeast Bre1, RNF20 and RNF40, were identified (4,5). These two proteins form a tight heterodimer that acts as the major E3 ligase responsible for histone H2B monoubiquitination at Lys120 in mammalian cells, a modification linked to RNA Pol II-dependent transcription elongation in undamaged cells. Researchers have shown that DNA double-strand breaks (DSBs) are also capable of inducing monoubiquitination of H2B. This process depends upon the recruitment to DSB sites, as well as ATM-dependent phosphorylation of the RNF20-RNF40 heterodimer, thus highlighting a role for this E3 ligase in DSB repair pathways (6). Indeed, investigators have shown that loss of RNF20-RNF40 function promotes replication stress and chromosomal instability, which may constitute an early step in malignant transformation that precedes cell invasion (7).

$260
100 µl
APPLICATIONS
REACTIVITY
Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Endogenous cannabinoids have been implicated in addictive behaviors and drug abuse (1). Fatty-acid amide hydrolase 1 (FAAH1) is a plasma membrane-bound hydrolase that converts oleamide to oleic acid (2). This hydrolase also converts the cannabinoid anandamide, the endogenous ligand for the CB1 cannabinoid receptor, to arachidonic acid, suggesting a role in fatty-acid amide inactivation (2). Mice lacking FAAH1 have significantly higher levels of anandamide in the brain and show decreased sensitivity to pain, further indicating a role for FAAH1 in the regulation of endocannabinoid signaling in vivo (3). FAAH1 null mice also demonstrate an increased preference for alcohol and an increased voluntary uptake of alcohol as compared to wild-type mice, indicating a role of FAAH1 in modulating addictive behaviors (1).

$262
3 nmol
300 µl
SignalSilence® Aurora A/AIK siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit Aurora A/AIK 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: Aurora kinases belong to a highly conserved family of mitotic serine/threonine kinases with three members identified among mammals: Aurora A, B, and C (1,2). Studies on the temporal expression pattern and subcellular localization of Aurora kinases in mitotic cells suggest an association with mitotic structure. Aurora kinase functional influences span from G2 phase to cytokinesis and may be involved in key cell cycle events such as centrosome duplication, chromosome bi-orientation and segregation, cleavage furrow positioning, and ingression (3). Aurora A is detected at the centrosomes, along mitotic spindle microtubules, and in the cytoplasm of mitotically proliferating cells. Aurora A protein levels are low during G1 and S phases and peak during the G2/M phase of the cell cycle. Phosphorylation of Aurora A at Thr288 in its catalytic domain increases kinase activity. Aurora A is involved in centrosome separation, maturation, and spindle assembly and stability. Expression of Aurora B protein also peaks during the G2/M phase of the cell cycle; Aurora B kinase activity peaks at the transition from metaphase to the end of mitosis. Aurora B associates with chromosomes during prophase prior to relocalizing to the spindle at anaphase. Aurora B regulates chromosome segregation through the control of microtubule-kinetochore attachment and cytokinesis. Expression of both Aurora A and Aurora B during the G2/M phase transition is tightly coordinated with histone H3 phosphorylation (4,5); research investigators have observed overexpression of these kinases in a variety of human cancers (2,4). Aurora C localizes to the centrosome from anaphase to cytokinesis and both mRNA and protein levels peak during G2/M phase. Although typical Aurora C expression is limited to the testis, research studies report overexpression of Aurora C is detected in various cancer cell lines (6).

$262
3 nmol
300 µl
SignalSilence® c-Raf siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit c-Raf 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: A-Raf, B-Raf, and c-Raf (Raf-1) are the main effectors recruited by GTP-bound Ras to activate the MEK-MAP kinase pathway (1). Activation of c-Raf is the best understood and involves phosphorylation at multiple activating sites including Ser338, Tyr341, Thr491, Ser494, Ser497, and Ser499 (2). p21-activated protein kinase (PAK) has been shown to phosphorylate c-Raf at Ser338, and the Src family phosphorylates Tyr341 to induce c-Raf activity (3,4). Ser338 of c-Raf corresponds to similar sites in A-Raf (Ser299) and B-Raf (Ser445), although this site is constitutively phosphorylated in B-Raf (5). Inhibitory 14-3-3 binding sites on c-Raf (Ser259 and Ser621) can be phosphorylated by Akt and AMPK, respectively (6,7). While A-Raf, B-Raf, and c-Raf are similar in sequence and function, differential regulation has been observed (8). Of particular interest, B-Raf contains three consensus Akt phosphorylation sites (Ser364, Ser428, and Thr439) and lacks a site equivalent to Tyr341 of c-Raf (8,9). Research studies have shown that the B-Raf mutation V600E results in elevated kinase activity and is commonly found in malignant melanoma (10). Six residues of c-Raf (Ser29, Ser43, Ser289, Ser296, Ser301, and Ser642) become hyperphosphorylated in a manner consistent with c-Raf inactivation. The hyperphosphorylation of these six sites is dependent on downstream MEK signaling and renders c-Raf unresponsive to subsequent activation events (11).

$262
3 nmol
300 µl
SignalSilence® PAK2 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit PAK2 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® PAK2 siRNA II from Cell Signaling Technology (CST) allows the researcher to specifically inhibit PAK2 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® S100A4 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit S100A4 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: Despite their relatively small size (8-12 kDa) and uncomplicated architecture, S100 proteins regulate a variety of cellular processes such as cell growth and motility, cell cycle progression, transcription, and differentiation. To date, 25 members have been identified, including S100A1-S100A18, trichohyalin, filaggrin, repetin, S100P, and S100Z, making it the largest group in the EF-hand, calcium-binding protein family. Interestingly, 14 S100 genes are clustered on human chromosome 1q21, a region of genomic instability. Research studies have demonstrated that significant correlation exists between aberrant S100 protein expression and cancer progression. S100 proteins primarily mediate immune responses in various tissue types but are also involved in neuronal development (1-4).Each S100 monomer bears two EF-hand motifs and can bind up to two molecules of calcium (or other divalent cation in some instances). Structural evidence shows that S100 proteins form antiparallel homo- or heterodimers that coordinate binding partner proximity in a calcium-dependent (and sometimes calcium-independent) manner. Although structurally and functionally similar, individual members show restricted tissue distribution, are localized in specific cellular compartments, and display unique protein binding partners, which suggests that each plays a specific role in various signaling pathways. In addition to an intracellular role, some S100 proteins have been shown to act as receptors for extracellular ligands or are secreted and exhibit cytokine-like activities (1-4).

$262
3 nmol
300 µl
SignalSilence® SirT6 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit SirT6 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 Silent Information Regulator (Sir2) family of genes is a highly conserved group of genes that encode nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylases, also known as class III histone deacetylases. The first discovered and best characterized of this family is Saccharomyces cerevisiae Sir2, which is involved in silencing of mating type loci, telomere maintenance, DNA damage response, and cell aging (1). SirT6, a mammalian homolog of Sir2, is a nuclear, chromatin-associated protein that promotes the normal maintenance of genome integrity mediated by the base excision repair (BER) pathway (2-4). The BER pathway repairs single-stranded DNA lesions that arise spontaneously from endogenous alkylation, oxidation, and deamination events. SirT6 deficient mice show increased sensitivity to DNA-damaging agents, including the alkylating agents MMS and H2O2 (2). In addition, these mice show genome instability with increased frequency of fragmented chromosomes, detached centromeres, and gaps (2). SirT6 may regulate the BER pathway by deacetylating DNA Polβ or other core components of the pathway (2).

$262
3 nmol
300 µl
SignalSilence® USP14 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit USP14 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. In humans, there are three proteasomal DUBs: PSMD14 (POH1/RPN11), UCH37 (UCH-L5), and Ubiquitin-Specific Protease 14, which is also known as the 60 kDa subunit of tRNA-guanine transglycosylase (USP14/TGT60 kDa). USP14 is recruited to the proteasome through its reversible association with the PSMD2 (S2/hRPN1) subunit of the 19S regulatory particle. Whereas PSMD14 appears to promote substrate degradation (3,4), USP14 is thought to antagonize substrate degradation (5-8). While the underlying mechanism for the opposing roles of these two proteasomal DUBs is still uncertain, it is thought that USP14 removes ubiquitin from substrate upon docking of the substrate with the 26S proteasome. Furthermore, USP14 trims ubiquitin residues from the distal end of the polyubiquitin chain, thus decreasing the affinity of the chain for the ubiquitin receptors of the proteasome, and allowing for enhanced substrate stability (6,9,10). Studies have elucidated a physiologic role for USP14 in regulating synaptic activity in mammals (11). Research studies have shown that targeting this activity with small molecule inhibitors has potential benefits for the treatment of neurodegenerative diseases and cancer (5,12).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Contactin-associated protein 2 (Caspr2) is a type I transmembrane protein and member of the neurexin superfamily that mediates nervous system cell-cell interactions through the Neurexin IV-Caspr-Paranodin (NCP) complex (1). A multiprotein complex consisting of TAG-1, Caspr2, K+ channel, PSD95 and protein 4.1B mediates the molecular interactions at the juxtaparanodal region of myelinated axons, with homophilic TAG-1 interactions mediating the binding of this complex to glia (2,3).Caspr2 protein localizes to juxtaparanodal regions of myelinated axons where it forms a cis-complex with the immunoglobulin-like cell adhesion molecule TAG-1. Caspr2 also binds to Shaker K+ channels Kv1.1, Kv1.2, and their Kvβ2 subunit. A PDZ domain at the Caspr2 carboxy terminus mediates the Caspr2-K+ channel association. Caspr2 is required for proper K+ channel localization, as Caspr2 deletion causes the redistribution of channels along the internodes (1-3). Furthermore, Caspr2 binds to protein 4.1B and connects the protein complex to the axonal cytoskeleton (4). Mutations in the Caspr2 gene have been linked to focal epilepsy, cortical dysplasia and Gilles de la Tourette syndrome (5,6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: DDX4 is an ATP-dependent DEAD-box RNA helicase found in the chromatoid body of the germ cells (1). This enzyme is specific to germ cells and is necessary for germ cell development (2). Mouse DDX4 was shown to interact with Dicer, suggesting a role in microRNA-mediated RNA silencing (1).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Chromatin IP, Immunoprecipitation, Western Blotting

Background: The super elongation complex (SEC) plays a critical role in regulating RNA polymerase II (RNAPII) transcription elongation (1). The SEC is composed of AFF4, AFF1/AF4, MLLT3/AF9, and MLLT1/ENL proteins. The pathogenesis of mixed lineage leukemia is often associated with translocations of the SEC subunits joined to the histone H3 Lys4 methyltransferase mixed lineage leukemia (MLL) gene (1-4). The SEC has been found to contain RNAPII elongation factors eleven-nineteen lysine-rich leukemia (ELL), ELL2, and ELL3, along with the associated factors EAF1 and EAF2, which can increase the catalytic rate of RNAPII transcription in vitro, (1,2,5-7). The SEC positive transcription elongation factor b (P-TEFb) phosphorylates the carboxy-terminal domain within the largest subunit of RNAP II at Ser2 of the heptapeptide repeat. The SEC negative transcription elongation factors, DRB-induced stimulating factor (DSIF) and negative elongation factor (NELF), signal the transition from transcription initiation and pausing to productive transcription elongation (2,8-10). The chromosomal translocation of MLL with the members of the SEC leads to SEC recruitment to MLL regulated genes, such as the highly developmentally regulated Hox genes, implicating the misregulation and overexpression of these genes as underlying contributors to leukemogenesis (1,2,9,11).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Macrophage inhibitory cytokine-1 (Mic-1), also termed GDF15 (1), PTGF-β (2), PLAB (3), PDF (4), and NAG-1 (5), is a divergent member of the transforming growth factor-β (TGF-β) superfamily (6). Like other family members, Mic-1 is synthesized as an inactive precursor that undergoes proteolytic processing involving removal of an N-terminal hydrophobic signal sequence followed by cleavage at a conserved RXXR site generating an active C-terminal domain that is secreted as a dimeric protein. Mic-1 is highly expressed in the placenta and is also dramatically increased by cellular stress, acute injury, inflammation, and cancer. In the brain, Mic-1 is found in the choroid plexus and is secreted into the cerebrospinal fluid (7). It is also a transcriptional target of the p53 tumor suppressor protein and may serve as a biomarker for p53 activity (8,9). During tumor progression, Mic-1 has various effects on apoptosis, differentiation, angiogenisis, and metastasis, and may also contribute to weight loss during cancer (10,11).