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Product listing: PAX5 (D19F8) XP® Rabbit mAb, UniProt ID Q02548 #8970 to PD-L1 (E1L3N®) XP® Rabbit mAb (HRP Conjugate), UniProt ID Q9NZQ7 #51296

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

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

Background: Paired box (PAX) proteins are a family of transcription factors that play important and diverse roles in animal development (1). Nine PAX proteins (PAX1-9) have been described in humans and other mammals. They are defined by the presence of an amino-terminal "paired" domain, consisting of two helix-turn-helix motifs, with DNA binding activity (2). PAX proteins are classified into four structurally distinct subgroups (I-IV) based on the absence or presence of a carboxy-terminal homeodomain and a central octapeptide region. Subgroup I (PAX1 and 9) contains the octapeptide but lacks the homeodomain; subgroup II (PAX2, 5, and 8) contains the octapeptide and a truncated homeodomain; subgroup III (PAX3 and 7) contains the octapeptide and a complete homeodomain; and subgroup IV (PAX4 and 6) contains a complete homeodomain but lacks the octapeptide region (2). PAX proteins play critically important roles in development by regulating transcriptional networks responsible for embryonic patterning and organogenesis (3); a subset of PAX proteins also maintain functional importance during postnatal development (4). Research studies have implicated genetic mutations that result in aberrant expression of PAX genes in a number of cancer subtypes (1-3), with members of subgroups II and III identified as potential mediators of tumor progression (2).

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

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

Background: The dynamic polymerization and depolymerization of actin filaments, a process governed by external and internal signaling events, is vital for cell motility (immune cell function, migration, invasion, metastasis, angiogenesis), cell division and adhesion. Among the many regulators of actin dynamics are profilins. Profilins are conserved actin binding proteins that affect the rate of actin polymerization by binding actin monomers and promoting the exchange of ADP for ATP (reviewed in 1). Profilins bind to proteins involved in the regulation of actin dynamics including palladin (2), dynamin-1 (3), VASP (4) and N-WASP (5). In mice, knockout of the ubiquitously expressed profilin-1 indicates that the protein is essential for embryonic development (6). Profilin-2 is primarily expressed in brain and functions in the regulation of neurite outgrowth (7), membrane trafficking and endocytosis (3). The recently cloned profilin-3 is expressed in kidney and testes (8).

$305
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 Btk (D3H5) Rabbit mAb #8547.
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Flow Cytometry

Background: Bruton's tyrosine kinase (Btk) is a member of the Btk/Tec family of cytoplasmic tyrosine kinases. Like other Btk family members, it contains a pleckstrin homology (PH) domain and Src homology SH3 and SH2 domains. Btk plays an important role in B cell development (1,2). Activation of B cells by various ligands is accompanied by Btk membrane translocation mediated by its PH domain binding to phosphatidylinositol-3,4,5-trisphosphate (3-5). The membrane-localized Btk is active and associated with transient phosphorylation of two tyrosine residues, Tyr551 and Tyr223. Tyr551 in the activation loop is transphosphorylated by the Src family tyrosine kinases, leading to autophosphorylation at Tyr223 within the SH3 domain, which is necessary for full activation (6,7). The activation of Btk is negatively regulated by PKCβ through phosphorylation of Btk at Ser180, which results in reduced membrane recruitment, transphosphorylation, and subsequent activation (8). The PKC inhibitory signal is likely to be a key determinant of the B cell receptor signaling threshold to maintain optimal Btk activity (8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

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

Background: Heat shock protein (HSP) 27 is one of the small HSPs that are constitutively expressed at different levels in various cell types and tissues. Like other small HSPs, HSP27 is regulated at both the transcriptional and posttranslational levels (1). In response to stress, the HSP27 expression increases several-fold to confer cellular resistance to the adverse environmental change. HSP27 is phosphorylated at Ser15, Ser78, and Ser82 by MAPKAPK-2 as a result of the activation of the p38 MAP kinase pathway (2,3). Phosphorylation of HSP27 causes a change in its tertiary structure, which shifts from large homotypic multimers to dimers and monomers (4). It has been shown that phosphorylation and increased concentration of HSP27 modulates actin polymerization and reorganization (5,6).

$303
100 µl
$717
300 µl
APPLICATIONS
REACTIVITY
D. melanogaster, Human, Monkey, Mouse, Rat

Application Methods: Chromatin IP, Immunoprecipitation, Western Blotting

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).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

Background: Villin is a member of the gelsolin family of calcium-regulated actin-binding proteins. Unlike the ubiquitously expressed gelsolin, villin expression is restricted to simple epithelia of the gastrointestinal and urogenital tracts. It is localized to the apical cytoplasm and brush borders of these cells. Villin functions in the regulation of actin dynamics in the apical epithelium, capping, nucleating and/or severing actin filaments in a calcium-dependent manner and regulating cell shape in response to external stimuli (1,2). Phosphorylation of villin at Tyr60, 81 and 256 may be involved in the regulation of cell migration (3). Expression of villin is increased in colorectal cancers (4), and villin1 function appears to be involved in progressive cholestasis and hepatic failure (5).

$348
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 647 fluorescent dye and tested in-house for direct flow cytometry analysis in human cells. The antibody is expected to exhibit the same species cross-reactivity as the unconjugated PDGF Receptor α (D13C6) XP® Rabbit mAb #5241.
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry

Background: Platelet derived growth factor (PDGF) family proteins exist as several disulphide-bonded, dimeric isoforms (PDGF AA, PDGF AB, PDGF BB, PDGF CC, and PDGF DD) that bind in a specific pattern to two closely related receptor tyrosine kinases, PDGF receptor α (PDGFRα) and PDGF receptor β (PDGFRβ). PDGFRα and PDGFRβ share 75% to 85% sequence homology between their two intracellular kinase domains, while the kinase insert and carboxy-terminal tail regions display a lower level (27% to 28%) of homology (1). PDGFRα homodimers bind all PDGF isoforms except those containing PDGF D. PDGFRβ homodimers bind PDGF BB and DD isoforms, as well as the PDGF AB heterodimer. The heteromeric PDGF receptor α/β binds PDGF B, C, and D homodimers, as well as the PDGF AB heterodimer (2). PDGFRα and PDGFRβ can each form heterodimers with EGFR, which is also activated by PDGF (3). Various cells differ in the total number of receptors present and in the receptor subunit composition, which may account for responsive differences among cell types to PDGF binding (4). Ligand binding induces receptor dimerization and autophosphorylation, followed by binding and activation of cytoplasmic SH2 domain-containing signal transduction molecules, such as GRB2, Src, GAP, PI3 kinase, PLCγ, and NCK. A number of different signaling pathways are initiated by activated PDGF receptors and lead to control of cell growth, actin reorganization, migration, and differentiation (5). Tyr751 in the kinase-insert region of PDGFRβ is the docking site for PI3 kinase (6). Phosphorylated pentapeptides derived from Tyr751 of PDGFRβ (pTyr751-Val-Pro-Met-Leu) inhibit the association of the carboxy-terminal SH2 domain of the p85 subunit of PI3 kinase with PDGFRβ (7). Tyr740 is also required for PDGFRβ-mediated PI3 kinase activation (8).

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Lactate dehydrogenase (LDH) catalyzes the interconversion of pyruvate and NADH to lactate and NAD+. When the oxygen supply is too low for mitochondrial ATP production, this reaction recycles NADH generated in glycolysis to NAD+, which reenters glycolysis. The major form of LDH found in muscle cells is the A (LDHA) isozyme. The LDHA promoter contains HIF-1α binding sites (1). LDHA expression is induced under hypoxic conditions (2). During intensive and prolonged muscle exercise, lactate accumulates in muscle cells when the supply of oxygen does not meet demand. When oxygen levels return to normal, LDH converts lactate to pyruvate to generate ATP in the mitochondrial electron transport chain.

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

Application Methods: Western Blotting

Background: CAD is essential for the de novo synthesis of pyrimidine nucleotides and possesses the following enzymatic activities: glutamine amidotransferase, carbamoyl-phosphate synthetase, aspartate transcarbamoylase, and dihydroorotase. Thus, the enzyme converts glutamine to uridine monophosphate, a common precursor of all pyrimidine bases, and it is necessary for nucleic acid synthesis (1). In resting cells, CAD is localized mainly in the cytoplasm where it carries out pyrimidine synthesis. As proliferating cells enter S phase, MAP Kinase (Erk1/2) phosphorlyates CAD at Thr456, resulting in CAD translocation to the nucleus. As cells exit S phase, CAD is dephosphorylated at Thr456 and phosphorylated at Ser1406 by PKA, returning the pathway to basal activity (2). Various research studies have shown increased expression of CAD in several types of cancer, prompting the development of pharmacological inhibitors such as PALA. Further studies have identified CAD as a potential predictive early marker of prostate cancer relapse (3).

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

Application Methods: Chromatin IP, Immunoprecipitation, Western Blotting

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

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

Application Methods: Immunohistochemistry (Paraffin), Western Blotting

Background: Class A basic helix-loop-helix protein 15 (MIST1, bHLHa15) is a highly conserved basic helix loop helix family transcription factor that binds E-box motifs and regulates the expression of developmentally regulated genes (1). MIST1 can bind DNA as a homodimer, or may heterodimerize with other bHLH proteins to regulate target gene expression (1). MIST1 is expressed in an array of tissues, including salivary glands, stomach, small intestine, and the pancreas, but is generally restricted to secretory cell subtypes (2). In the pancreas, MIST1 is essential for the maturation, maintenance, and function of acinar cells (3). In gastric chief cells, MIST1 regulates the expression of RAB26 and RAB3D, two GTPases that function to regulate secretory granule formation (4). Loss of MIST1 in gastric chief cells may be a potential marker of gastric epithelial neoplasia (5).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Mcl-1 is an anti-apoptotic member of the Bcl-2 family originally isolated from the ML-1 human myeloid leukemia cell line during phorbol ester-induced differentiation along the monocyte/macrophage pathway (1). Similar to other Bcl-2 family members, Mcl-1 localizes to the mitochondria (2), interacts with and antagonizes pro-apoptotic Bcl-2 family members (3), and inhibits apoptosis induced by a number of cytotoxic stimuli (4). Mcl-1 differs from its other family members in its regulation at both the transcriptional and post-translational level. First, Mcl-1 has an extended amino-terminal PEST region, which is responsible for its relatively short half-life (1,2). Second, unlike other family members, Mcl-1 is rapidly transcribed via a PI3K/Akt dependent pathway, resulting in its increased expression during myeloid differentiation and cytokine stimulation (1,5-7). Mcl-1 is phosphorylated in response to treatment with phorbol ester, microtubule-damaging agents, oxidative stress, and cytokine withdrawal (8-11). Phosphorylation at Thr163, the conserved MAP kinase/ERK site located within the PEST region, slows Mcl-1 protein turnover (10) but may prime the GSK-3 mediated phosphorylation at Ser159 that leads to Mcl-1 destabilization (11). Mcl-1 deficiency in mice results in peri-implantation lethality (12). In addition, conditional disruption of the corresponding mcl-1 gene shows that Mcl-1 plays an important role in early lymphoid development and in the maintenance of mature lymphocytes (13).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: PTEN (phosphatase and tensin homologue deleted on chromosome ten), also referred to as MMAC (mutated in multiple advanced cancers) phosphatase, is a tumor suppressor implicated in a wide variety of human cancers (1). PTEN encodes a 403 amino acid polypeptide originally described as a dual-specificity protein phosphatase (2). The main substrates of PTEN are inositol phospholipids generated by the activation of the phosphoinositide 3-kinase (PI3K) (3). PTEN is a major negative regulator of the PI3K/Akt signaling pathway (1,4,5). PTEN possesses a carboxy-terminal, noncatalytic regulatory domain with three phosphorylation sites (Ser380, Thr382, and Thr383) that regulate PTEN stability and may affect its biological activity (6,7). PTEN regulates p53 protein levels and activity (8) and is involved in G protein-coupled signaling during chemotaxis (9,10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse

Application Methods: Immunoprecipitation, Western Blotting

Background: CBP (CREB-binding protein) and p300 are highly conserved and functionally related transcriptional co-activators that associate with transcriptional regulators and signaling molecules, integrating multiple signal transduction pathways with the transcriptional machinery (1,2). CBP/p300 also contain histone acetyltransferase (HAT) activity, allowing them to acetylate histones and other proteins (2). Phosphorylation of p300 at Ser89 by PKC represses its transciptional acitivity, and phosphorylation at the same site by AMPK disrupts the association of p300 with nuclear receptors (3,4). Ser1834 phosphorylation of p300 by Akt disrupts its association with C/EBPβ (5). Growth factors induce phosphorylation of CBP at Ser437, which is required for CBP recruitment to the transcription complex (6). CaM kinase IV phosphorylates CBP at Ser302, which is required for CBP-dependent transcriptional activation in the CNS (7). The role of acetylation of CBP/p300 is of particular interest (2,8). Acetylation of p300 at Lys1499 has been demonstrated to enhance its HAT activity and affect a wide variety of signaling events (9).

$122
20 µl
$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, 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).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Insulin-like growth factor-binding proteins (IGFBPs) play an integral role in modifying insulin-like growth factor (IGF) actions in a wide variety of cell types. This family contains six members that are structurally related but encoded by distinct genes. IGFBPs have a high affinity for IGFs. Some members of the IGFBP family have been consistently shown to inhibit IGF actions by preventing them from gaining access to the IGF receptors, while others potentiate IGF actions by facilitating the ligand-receptor interaction (1-3). IGFBP2 is the second most abundant IGFBP in the circulation and is present in various other biological fluids and tissues of many vertebrate species. Serum IGFBP2 levels are elevated in conditions such as shock, fasting, hypoxemia or after traumata, suggesting complex regulation of IGFBP2 expression (4). IGFBP2 is overexpressed in many malignancies and is often correlated with an increasingly malignant status of the tumor, pointing to a potential involvement of IGFBP2 in tumorigenesis (5).

$293
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

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

Background: Keratins (cytokeratins) are intermediate filament proteins that are mainly expressed in epithelial cells. Keratin heterodimers composed of an acidic keratin (or type I keratin, keratins 9 to 23) and a basic keratin (or type II keratin, keratins 1 to 8) assemble to form filaments (1,2). Keratin isoforms demonstrate tissue- and differentiation-specific profiles that make them useful as research biomarkers (1). Research studies have shown that mutations in keratin genes are associated with skin disorders, liver and pancreatic diseases, and inflammatory intestinal diseases (3-6).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

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

Background: The ephrin receptor B2 (EphB2) is an ephrin family receptor tyrosine kinase that plays an important role in regulating growth and development of multiple tissues and organs (1,2). The EphB2 transmembrane receptor protein contains a kinase domain, a PDZ motif, and a SAM domain within a conserved cytoplasmic domain. A ligand binding domain, a cysteine-rich domain, and fibronectin type III repeats comprise the conserved EphB2 extracellular domain (3). EphB2 binds with high affinity to ephrin B ligands, and to some ephrin A proteins, to initiate bidirectional signaling between neighboring cells (1,2). Upon binding, EphB2-Ephrin B2 dimers form a heterotetramer and position the receptor-ligand complex on the cell membrane to facilitate bidirectional signal transduction (3). In addition to associating with ephrin ligands, EphB2 also regulates a number of biological processes through interaction with focal adhesion kinase (FAK), NMDA receptor (NMDAR), the Rac1 guanine nucleotide exchange factor Tiam1, and p21-activated kinase (PAK1) (4-7). While some studies support a role for EphB2 as a pro-oncogenic kinase, other research suggests that EphB2 acts as a tumor suppressor (1,2,4,8).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Immunoprecipitation, Western Blotting

Background: The methylation state of lysine residues in histone proteins is a major determinant for formation of active and inactive regions of the genome and is crucial for proper programming of the genome during development (1,2). Jumonji C (JmjC) domain-containing proteins represent the largest class of potential histone demethylase proteins (3). The JmjC domain can catalyze the demethylation of mono-, di-, and tri-methyl lysine residues via an oxidative reaction that requires iron and α-ketoglutarate (3). Based on homology, both humans and mice contain at least 30 such proteins, which can be divided into 7 separate families (3). The JARID (Jumonji/AT-rich interactive domain-containing protein) family contains four members: JARID1A (also RBP2 and RBBP2), JARID1B (also PLU-1), JARID1C (also SMCX) and JARID1D (also SMCY) (4). In addition to the JmJC domain, these proteins contain JmJN, BRIGHT, C5HC2 zinc-finger, and PHD domains, the latter of which binds to methylated histone H3 (Lys9) (4). All four JARID proteins demethylate di- and tri-methyl histone H3 Lys4; JARID1B also demethylates mono-methyl histone H3 Lys4 (5-7). JARID1A is a critical RB-interacting protein and is required for Polycomb-Repressive Complex 2 (PRC2)-mediated transcriptional repression during ES cell differentiation (8). A JARID1A-NUP98 gene fusion is associated with myeloid leukemia (9). JARID1B, which interacts with many proteins including c-Myc and HDAC4, may play a role in cell fate decisions by blocking terminal differentiation (10-12). JARID1B is over-expressed in many breast cancers and may act by repressing multiple tumor suppressor genes including BRCA1 and HOXA5 (13,14). JARID1C has been found in a complex with HDAC1, HDAC2, G9a and REST, which binds to and represses REST target genes in non-neuronal cells (7). JARID1C mutations are associated with X-linked mental retardation and epilepsy (15,16). JARID1D is largely uncharacterized.

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

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

Background: The NF-κB/Rel transcription factors are present in the cytosol in an inactive state, complexed with the inhibitory IκB proteins (1-3). Most agents that activate NF-κB do so through a common pathway based on phosphorylation-induced, proteasome-mediated degradation of IκB (3-7). The key regulatory step in this pathway involves activation of a high molecular weight IκB kinase (IKK) complex whose catalysis is generally carried out by three tightly associated IKK subunits. IKKα and IKKβ serve as the catalytic subunits of the kinase and IKKγ serves as the regulatory subunit (8,9). Activation of IKK depends upon phosphorylation at Ser177 and Ser181 in the activation loop of IKKβ (Ser176 and Ser180 in IKKα), which causes conformational changes, resulting in kinase activation (10-13).

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

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

Background: LIN28A and LIN28B are conserved, developmentally regulated RNA binding proteins that inhibit the processing and maturation of the let-7 family of miRNAs (1,2). The let-7 miRNAs have been implicated in repression of oncogenes such as Ras, Myc, and HMGA2 (3). It has recently been shown that upregulation of LIN28A and LIN28B in primary human tumors and human cancer cell lines is correlated with downregulation of let-7 miRNAs (4). LIN28 genes are reported to be involved in primordial germ cell development and germ cell malignancy (5). In addition, allelic variation in LIN28B is associated with regulating the timing of puberty in humans (6). Overexpression of LIN28A, in conjunction with Oct-4, Sox2, and Nanog, can reprogram human fibroblasts to pluripotent, ES-like cells (7).

$129
20 µl
$303
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

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

Background: The methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP) is an essential step in the formation of thymine nucleotides (1,2, reviewed in 3). This process is catalyzed by thymidylate synthase (TS or TYMS), a homodimer composed of two 30 kDa subunits. TS is an intracellular enzyme that provides the sole de novo source of thymidylate, making it a required enzyme in DNA biosynthesis with activity highest in proliferating cells (1). Being the exclusive source of dTMP, investigators have concluded that TS is also an important target for anticancer agents such as 5-fluorouracil (5-FU) (1-5). 5-FU acts as a TS inhibitor and is active against solid tumors such as colon, breast, head, and neck. Research studies have demonstrated that patients with metastases expressing lower levels of TS have a higher response rate to treatment with 5-FU than patients with tumors that have increased levels of TS (5). Researchers continue to investigate TS expression in different types of cancers (6-10).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Apoptosis signal-regulating kinase 1 (ASK1), a MAP kinase kinase kinase, plays essential roles in stress-induced apoptosis (1,2). ASK1 is activated in response to a variety of stress-related stimuli through distinct mechanisms and activates MKK4 and MKK3, which in turn activate JNK and p38 (3). Overexpression of ASK1 activates JNK and p38 and induces apoptosis in several cell types through signals involving the mitochondrial cell death pathway. Embryonic fibroblasts or primary neurons derived from ASK1-/- mice are resistant to stress-induced JNK and p38 activation as well as cell death (4,5). Phosphorylation at Ser967 is essential for ASK1 association with 14-3-3 proteins and suppression of cell death (6). Oxidative stress induces dephosphorylation of Ser967 and phosphorylation of Thr845 in the activation loop of ASK1, both of which are correlated with ASK1 activity and ASK1-dependent apoptosis (7,8). Akt phosphorylates ASK1 at Ser83, which attenuates ASK1 activity and promotes cell survival (9).

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Bovine, Human, Monkey, Mouse, Pig, Rat

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

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).

PTMScan® Technology employs a proprietary methodology from Cell Signaling Technology (CST) for peptide enrichment by immunoprecipitation using a specific bead-conjugated antibody in conjunction with liquid chromatography (LC) tandem mass spectrometry (MS/MS) for quantitative profiling of post-translational modification (PTM) sites in cellular proteins. These include phosphorylation (PhosphoScan®), ubiquitination (UbiScan®), acetylation (AcetylScan®), and methylation (MethylScan®), among others. PTMScan® Technology enables researchers to isolate, identify, and quantitate large numbers of post-translationally modified cellular peptides with a high degree of specificity and sensitivity, providing a global overview of PTMs in cell and tissue samples without preconceived biases about where these modified sites occur (1). For more information on PTMScan® Proteomics Services, please visit www.cellsignal.com/common/content/content.jsp?id=ptmscan-services.

Background: Arginine methylation is a prevalent PTM found on both nuclear and cytoplasmic proteins. Arginine methylated proteins are involved in many different cellular processes, including transcriptional regulation, signal transduction, RNA metabolism, and DNA damage repair (1-3). Arginine methylation is carried out by the arginine N-methyltransferase (PRMT) family of enzymes that catalyze the transfer of a methyl group from S-adenosylmethionine (AdoMet) to a guanidine nitrogen of arginine (4). There are three different types of arginine methylation: asymmetric dimethylarginine (aDMA, omega-NG,NG-dimethylarginine), where two methyl groups are placed on one of the terminal nitrogen atoms of the guanidine group of arginine; symmetric dimethylarginine (sDMA, omega-NG,N’G-dimethylarginine), where one methyl group is placed on each of the two terminal guanidine nitrogens of arginine; and monomethylarginine (MMA, omega-NG-dimethylarginine), where a single methyl group is placed on one of the terminal nitrogen atoms of arginine. Each of these modifications has potentially different functional consequences. Though all PRMT proteins catalyze the formation of MMA, Type I PRMTs (PRMT1, 3, 4, and 6) add an additional methyl group to produce aDMA, while Type II PRMTs (PRMT5 and 7) produce sDMA. Methylated arginine residues often reside in glycine-arginine rich (GAR) protein domains, such as RGG, RG, and RXR repeats (5). However, PRMT4/CARM1 and PRMT5 methylate arginine residues within proline-glycine-methionine rich (PGM) motifs (6).

$122
20 µl
$293
100 µl
APPLICATIONS
REACTIVITY
Dog, Hamster, Human, Monkey, Mouse, Rat

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

Background: The minichromosome maintenance (MCM) 2-7 proteins are a family of six related proteins required for initiation and elongation of DNA replication. MCM2-7 bind together to form the heterohexameric MCM complex that is thought to act as a replicative helicase at the DNA replication fork (1-5). This complex is a key component of the pre-replication complex (pre-RC) (reviewed in 1). Cdc6 and CDT1 recruit the MCM complex to the origin recognition complex (ORC) during late mitosis/early G1 phase forming the pre-RC and licensing the DNA for replication (reviewed in 2). Licensing of the chromatin permits the DNA to replicate only once per cell cycle, thereby helping to ensure that genetic alterations and malignant cell growth do not occur (reviewed in 3). Phosphorylation of the MCM2, MCM3, MCM4, and MCM6 subunits appears to regulate MCM complex activity and the initiation of DNA synthesis (6-8). CDK1 phosphorylation of MCM3 at Ser112 during late mitosis/early G1 phase has been shown to initiate complex formation and chromatin loading in vitro (8). Phosphorylation of MCM2 at serine 139 by cdc7/dbf4 coincides with the initiation of DNA replication (9). MCM proteins are removed during DNA replication, causing chromatin to become unlicensed through inhibition of pre-RC reformation. Studies have shown that the MCM complex is involved in checkpoint control by protecting the structure of the replication fork and assisting in restarting replication by recruiting checkpoint proteins after arrest (reviewed in 3,10).

$134
20 µl
$336
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

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

Background: Myristoylated Alanine-Rich C-Kinase Substrate (MARCKS) is a major PKC substrate expressed in many cell types. MARCKS has been implicated in cell motility, cell adhesion, phagocytosis, membrane traffic, and mitogenesis (1). PKC phosphorylates Ser159, 163, 167, and 170 of MARCKS in response to growth factors and oxidative stress. Phosphorylation at these sites regulates the calcium/calmodulin binding and filamentous (F)-actin cross-linking activities of MARCKS (2-4). Phosphorylation by PKC also results in translocation of MARCKS from the plasma membrane to the cytoplasm (5).

$364
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-TBK1/NAK (Ser172) (D52C2) XP® Rabbit mAb #5483.
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Flow Cytometry

Background: TBK1 (TANK-binding kinase 1)/NAK (NF-κB activating kinase) is an IκB kinase (IKK)-activating kinase and can activate IKK through direct phosphorylation (1). TBK1 was identified through association with the TRAF binding protein, TANK, and found to function upstream of NIK and IKK in the activation of NF-κB (2). TBK1 induces IκB degradation and NF-κB activity through IKKβ. TBK1 may mediate IKK and NF-κB activation in response to growth factors that stimulate PKCε activity (1). TBK1 plays a pivotal role in the activation of IRF3 in the innate immune response (3).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Immunoprecipitation, Western Blotting

Background: The Sestrin family of proteins, which comprises sestrin-1 (PA26), sestrin-2 (Hi95), and sestrin-3, plays an important role in regulating the cellular response to oxidative stress. Sestrin-1 and -2, both transcriptional targets of p53, have been shown to activate AMPK activity toward TSC2, ultimately resulting in the inhibition of mTOR (1). Thus, sestrin-1 and -2 link p53 signaling to the regulation of cellular growth (2). Sestrins have also been shown to function as modulators of cellular hydrogen peroxide concentration. Hydrogen peroxide is an important signaling molecule that is highly genotoxic and must therefore be tightly regulated (3). 2-Cys peroxiredoxins are metabolizing enzymes that maintain low cellular concentrations of hydrogen peroxide, but are hyperoxidized to an inactive state by a rapid increase in concentration (4) before quickly being reduced back to their active state by sestrins (5). This allows a hydrogen peroxide signal to temporarily circumvent the protective activity of 2-Cys peroxiredoxins, while minimizing oxidative damage.

$348
100 µl
This Cell Signaling Technology antibody is conjugated to the carbohydrate groups of horseradish peroxidase (HRP) via its amine groups. The HRP conjugated antibody is expected to exhibit the same species cross-reactivity as the unconjugated PD-L1 (E1L3N®) XP® Rabbit mAb #13684.
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

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