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Product listing: β-Catenin (L54E2) Mouse mAb (Alexa Fluor® 647 Conjugate), UniProt ID P35222 #4627 to MT1-MMP (D1E4) Rabbit mAb, UniProt ID P50281 #13130

$305
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 647 fluorescent dye and tested in-house for direct flow cytometry and immunofluorescent analysis in human cells.
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry)

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).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, 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).

$348
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 488 fluorescent dye and tested in-house for direct flow cytometric analysis in human cells. This antibody is expected to exhibit the same species cross-reactivity as the unconjugated Calreticulin (D3E6) XP® Rabbit mAb #12238.
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry)

Background: Calcium is a universal signaling molecule involved in many cellular functions such as cell motility, metabolism, protein modification, protein folding, and apoptosis. Calcium is stored in the endoplasmic reticulum (ER), where it is buffered by calcium binding chaperones such as calnexin and calreticulin, and is released via the IP3 Receptor channel (1). Calreticulin also functions as an ER chaperone that ensures proper folding and quality control of newly synthesized glycoproteins. As such, calreticulin presumably does not alter protein folding but regulates proper timing for efficient folding and subunit assembly. Furthermore, calreticulin retains proteins in non-native conformation within the ER and targets them for degradation (2,3).

The Class II HDAC Antibody Sampler Kit provides an economical means of detecting Class II HDAC proteins using control antibodies against HDAC4, HDAC5, HDAC6, and HDAC7. The kit contains enough primary antibodies to perform at least two western blot experiments.

Background: Acetylation of the histone tail causes chromatin to adopt an "open" conformation, allowing increased accessibility of transcription factors to DNA. The identification of histone acetyltransferases (HATs) and their large multiprotein complexes has yielded important insights into how these enzymes regulate transcription (1,2). HAT complexes interact with sequence-specific activator proteins to target specific genes. In addition to histones, HATs can acetylate nonhistone proteins, suggesting multiple roles for these enzymes (3). In contrast, histone deacetylation promotes a "closed" chromatin conformation and typically leads to repression of gene activity (4). Mammalian histone deacetylases can be divided into three classes on the basis of their similarity to various yeast deacetylases (5). Class I proteins (HDACs 1, 2, 3, and 8) are related to the yeast Rpd3-like proteins, those in class II (HDACs 4, 5, 6, 7, 9, and 10) are related to yeast Hda1-like proteins, and class III proteins are related to the yeast protein Sir2. Inhibitors of HDAC activity are now being explored as potential therapeutic cancer agents (6,7).

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

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

Background: Glucocorticoid hormones control cellular proliferation, inflammation, and metabolism through their association with the glucocorticoid receptor (GR)/NR3C1, a member of the nuclear hormone receptor superfamily of transcription factors (1). GR is composed of several conserved structural elements, including a carboxy-terminal ligand-binding domain (which also contains residues critical for receptor dimerization and hormone-dependent gene transactivation), a neighboring hinge region containing nuclear localization signals, a central zinc-finger-containing DNA-binding domain, and an amino-terminal variable region that participates in ligand-independent gene transcription. In the absence of hormone, a significant population of GR is localized to the cytoplasm in an inactive form via its association with regulatory chaperone proteins, such as HSP90, HSP70, and FKBP52. On hormone binding, GR is released from the chaperone complex and translocates to the nucleus as a dimer to associate with specific DNA sequences termed glucocorticoid response elements (GREs), thereby enhancing or repressing transcription of specific target genes (2). It was demonstrated that GR-mediated transcriptional activation is modulated by phosphorylation (3-5). Although GR can be basally phosphorylated in the absence of hormone, it becomes hyperphosphorylated upon binding receptor agonists. It has been suggested that hormone-dependent phosphorylation of GR may determine target promoter specificity, cofactor interaction, strength and duration of receptor signaling, receptor stability, and receptor subcellular localization (3).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Type I insulin-like growth factor receptor (IGF-IR) is a transmembrane receptor tyrosine kinase that is widely expressed in many cell lines and cell types within fetal and postnatal tissues (1-3). Receptor autophosphorylation follows binding of the IGF-I and IGF-II ligands. Three tyrosine residues within the kinase domain (Tyr1131, Tyr1135, and Tyr1136) are the earliest major autophosphorylation sites (4). Phosphorylation of these three tyrosine residues is necessary for kinase activation (5,6). Insulin receptors (IRs) share significant structural and functional similarity with IGF-I receptors, including the presence of an equivalent tyrosine cluster (Tyr1146/1150/1151) within the kinase domain activation loop. Tyrosine autophosphorylation of IRs is one of the earliest cellular responses to insulin stimulation (7). Autophosphorylation begins with phosphorylation at Tyr1146 and either Tyr1150 or Tyr1151, while full kinase activation requires triple tyrosine phosphorylation (8).

$305
400 µl
This Cell Signaling Technology antibody is immobilized via covalent binding of primary amino groups to N-hydroxysuccinimide (NHS)-activated sepharose beads. Rictor (D16H9) Rabbit mAb (Sepharose Bead Conjugate) is useful for immunoprecipitation assays. The antibody is expected to exhibit the same species cross-reactivity as the unconjugated Rictor (D16H9) Rabbit mAb #9476.
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Immunoprecipitation

Background: Cell growth is a fundamental biological process whereby cells accumulate mass and increase in size. The mammalian TOR (mTOR) pathway regulates growth by coordinating energy and nutrient signals with growth factor-derived signals (1). mTOR is a large protein kinase with two different complexes. One complex contains mTOR, GβL and raptor, which is a target of rapamycin. The other complex, insensitive to rapamycin, includes mTOR, GβL, Sin1, and rictor (1). The mTOR-rictor complex phosphorylates Ser473 of Akt/PKB in vitro (2). This phosphorylation is essential for full Akt/PKB activation. Furthermore, an siRNA knockdown of rictor inhibits Ser473 phosphorylation in 3T3-L1 adipocytes (3). This complex has also been shown to phosphorylate the rapamycin-resistant mutants of S6K1, another effector of mTOR (4).

$305
50 tests
100 µl
This Cell Signaling Technology antibody is conjugated to Alexa Fluor® 647 fluorescent dye and tested in-house for direct immunofluorescence of rat cells. The unconjugated antibody #3670 reacts with human, mouse and rat GFAP protein. CST expects that GFAP (GA5) Mouse mAb (Alexa Fluor® 647 Conjugate) will also recognize GFAP in these species.
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunofluorescence (Frozen)

Background: The cytoskeleton consists of three types of cytosolic fibers: microfilaments (actin filaments), intermediate filaments, and microtubules. Major types of intermediate filaments are specifically expressed in particular cell types: cytokeratins in epithelial cells, glial fibrillary acidic protein (GFAP) in glial cells, desmin in skeletal, visceral, and certain vascular smooth muscle cells, vimentin in cells of mesenchymal origin, and neurofilaments in neurons. GFAP and vimentin form intermediate filaments in astroglial cells and modulate their motility and shape (1). In particular, vimentin filaments are present at early developmental stages, while GFAP filaments are characteristic of differentiated and mature brain astrocytes. Thus, GFAP is commonly used as a marker for intracranial and intraspinal tumors arising from astrocytes (2). In addition, GFAP intermediate filaments are also present in nonmyelin-forming Schwann cells in the peripheral nervous system (3).

$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: 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
$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Immunoprecipitation, Western Blotting

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: Immunoprecipitation, Western Blotting

Background: N-myc downstream-regulated gene 1 (NDRG1), also termed Cap43, Drg1, RTP/rit42, and Proxy-1, is a member of the NDRG family, which is composed of four members (NDRG1-4) that function in growth, differentiation, and cell survival (1-5). NDRG1 is ubiquitously expressed and highly responsive to a variety of stress signals including DNA damage (4), hypoxia (5), and elevated levels of nickel and calcium (2). Expression of NDRG1 is elevated in N-myc defective mice and is negatively regulated by N- and c-myc (1,6). During DNA damage, NDRG1 is induced in a p53-dependent fashion and is necessary for p53-mediated apoptosis (4,7). Research studies have shown that NDRG1 may also play a role in cancer progression by promoting differentiation, inhibiting growth, and modulating metastasis and angiogenesis (3,4,6,8,9). Nonsense mutation of the NDRG1 gene has been shown to cause hereditary motor and sensory neuropathy-Lom (HMSNL), which is supported by studies demonstrating the role of NDRG1 in maintaining myelin sheaths and axonal survival (10,11). NDRG1 is up-regulated during mast cell maturation and its deletion leads to attenuated allergic responses (12). Both NDRG1 and NDRG2 are substrates of SGK1, although the precise physiological role of SGK1-mediated phosphorylation is not known (13). NDRG1 is phosphorylated by SGK1 at Thr328, Ser330, Thr346, Thr356, and Thr366. Phosphorylation by SGK1 primes NDRG1 for phosphorylation by GSK-3.

$129
20 µl
$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunohistochemistry (Paraffin), Western Blotting

Background: The Hepatocyte Growth Factor (HGF, also known as Scatter Factor) was initially discovered as a mitogenic cytokine that induced hepatocyte replication and proliferation (1-3). HGF is produced by stromal cells where it is processed by extracellular serine proteases into a heterodimer consisting of alpha and beta subunits (4). Through activation of its receptor, cMET, HGF has a wide range of effects beyond hepatocytes that includes angiogenesis, epithelial cell proliferation and morphogenesis, and tissue protection and regeneration (5). The HGF-cMET axis has been associated with several diseases, including cancer, where HGF has been shown to promote invasion, metastasis, and drug resistance (6,7). These research studies suggest that HGF is a potential diagnostic and therapeutic target.

$260
100 µl
APPLICATIONS
REACTIVITY
Human

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

Background: S100A8 and S100A9 are calcium-binding proteins that form a noncovalent heterodimer present in monocytes, neutrophils, macrophages, and some epithelial cells (1, 2). S100A8 and S100A9 are secreted by a tubulin-dependent mechanism during inflammatory conditions and have antimicrobial and chemotactic functions (3-5). Extracellular S100A8/S100A9 also induces an inflammatory response in endothelial cells, including induction of proinflammatory chemokines and adhesion molecules and increased vascular permeability (6). S100A8/S100A9 induces and recruits myeloid-derived suppressor cells (MDSC) in tumor-bearing mice (7). MDSC produce additional S100A8/S100A9 themselves, resulting in a positive feedback mechanism that sustains MDSC accumulation (7). S100A8/S100A9 is also highly expressed in psoriatic skin, where it directly upregulates transcription of complement protein C3, which contributes to disease (8). In addition, tumor-infiltrating myeloid cells induce expression of S100A8 and S100A9 in cancer cells, which increases invasiveness and metastasis (9).

$271
500 assays (96 well format)
1 Kit
The Mitochondrial Membrane Potential Assay Kit (II) is a fluorescent assay that detects the mitochondrial membrane potential in living cells. The kit includes the cationic dye TMRE (tetramethylrhodamine ethyl ester perchlorate) and a mitochondrial membrane potential disruptor CCCP (carbonyl cyanide 3-chlorophenylhydrazone). TMRE is a cell membrane permeable, fluorescent dye that accumulates in intact mitochondria. Depolarized or inactive mitochondria exhibit decreased membrane potential, resulting in reduced TMRE accumulation.
APPLICATIONS

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry)

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

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

Background: Ca2+ is a key second messenger in many intracellular signaling pathways. Ca2+ signals control many cellular functions ranging from short-term responses such as contraction and secretion to longer-term regulation of cell growth and proliferation (1,2). Stromal interaction molecules (STIMs) function as Ca2+ sensors that detect changes in Ca2+ content in intracellular Ca2+ stores (3). STIM1 is conserved, ubiquitously expressed, and functions as an endoplasmic reticulum (ER) Ca2+ sensor that migrates from the ER Ca2+ store to the plasma membrane where it activates calcium-release-activated calcium (CRAC) channels when the ER Ca2+ store is low (4). STIM1 is a potential tumor suppressor; defects in STIM1 may cause rhabdomyosarcoma and rhabdoid tumors (5). STIM1 can either homodimerize or form heterodimers with STIM2. STIM2 possesses a high sequence identity to STIM1 and can function as an inhibitor of STIM1-mediated plasma membrane store-operated Ca2+ entry (6). However, further investigation is required to elucidate the true physiological function of STIM2.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

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

Background: Glutamatergic neurons release glutamate, the most common excitatory neurotransmitter. Their synaptic vesicles are filled with glutamate by vesicular glutamate transporters, VGLUTs (1). VGLUT1, also called solute carrier family 17 member 7 (SLC17A7), was first identified as an inorganic phosphate transporter (2). Despite the absence of homology with neurotransmitter transporters, VGLUT1 was later demonstrated to be a glutamate transporter (1) specific to glutamatergic neurons (3). Closely related to VGLUT1, VGLUT2 and VGLUT3 are also involved in glutamate uptake into synaptic vesicles, but define different neuronal subpopulations (4,5). VGLUT1 and VGLUT2 are the most abundant isoforms. VGLUT1 is expressed in the cortex, hippocampus, and cerebellar cortex, while VGLUT2 is mostly found in the thalamus (6,7). VGLUT3 is expressed in hair cells of the auditory system (8).

$260
100 µl
APPLICATIONS
REACTIVITY
Bovine, Hamster, Human, Monkey, Pig, Rat

Application Methods: Western Blotting

Background: HSP70 and HSP90 are molecular chaperones expressed constitutively under normal conditions to maintain protein homeostasis and are induced upon environmental stress (1). Both HSP70 and HSP90 are able to interact with unfolded proteins to prevent irreversible aggregation and catalyze the refolding of their substrates in an ATP- and co-chaperone-dependent manner (1). HSP70 has a broad range of substrates including newly synthesized and denatured proteins, while HSP90 tends to have a more limited subset of substrates, most of which are signaling molecules. HSP70 and HSP90 often function collaboratively in a multi-chaperone system, which requires a minimal set of co-chaperones: HSP40, Hop, and p23 (2,3). The co-chaperones either regulate the intrinsic ATPase activity of the chaperones or recruit chaperones to specific substrates or subcellular compartments (1,4). When the ubiquitin ligase CHIP associates with the HSP70/HSP90 complex as a cofactor, the unfolded substrates are subjected to degradation by the proteasome (4). The biological functions of HSP70/HSP90 extend beyond their chaperone activity. They are essential for the maturation and inactivation of nuclear hormones and other signaling molecules (1,3). They also play a role in vesicle formation and protein trafficking (2).

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

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

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.

$260
100 µl
APPLICATIONS
REACTIVITY
Mouse, Rat

Application Methods: Immunofluorescence (Frozen), Western Blotting

Background: Bassoon (BSN), named such to underline its presumptive role in orchestrating events of the synaptic vesicle cycle (1), is a very large coiled-coil protein and is one of the core components of the cytomatrix at the active zones of both excitatory and inhibitory synapses (2). BSN is a scaffold protein that is a component of the synaptic ribbon, an electron-dense structure anchored at the active zone that tethers synaptic vesicles. Genetic disruption of BSN displaces the anchoring of ribbons to the active zones of photoreceptors and cochlear inner hair cells (3), and this displacement of the ribbons substantially impairs synaptic transmission, suggesting that, when present, BSN is important for the vesicle cycle (4).

$122
20 µl
$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: The c-Cbl proto-oncogene is a ubiquitously expressed cytoplasmic adaptor protein that is especially predominant in hematopoietic cells (1,2). c-Cbl is rapidly tyrosine-phosphorylated in response to stimulation of a variety of cell-surface receptors and becomes associated with a number of intracellular signaling molecules such as protein tyrosine kinases, phosphatidylinositol-3 kinase, Crk, and 14-3-3 proteins (3,4). c-Cbl possesses a highly conserved amino-terminal phosphotyrosine binding domain (TKB) and a C3HC4 RING finger motif. The TKB recognizes phosphorylated tyrosines on activated receptor tyrosine kinases (RTKs) as well as other nonreceptor tyrosine kinases. The RING finger motif recruits ubiquitin-conjugating enzymes. These two domains are primarily responsible for the ubiquitin ligase activity of c-Cbl and downregulation of RTKs (3). Research studies have indicated that in human cancer tissues, c-Cbl is frequently tyrosine-phosphorylated in a tumor-specific manner (5). Phosphorylation of Tyr731 of c-Cbl provides a docking site for downstream signaling components such as p85 and Fyn (6).

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

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

Background: Notch proteins (Notch1-4) are a family of transmembrane receptors that play important roles in development and the determination of cell fate (1). Mature Notch receptors are processed and assembled as heterodimeric proteins, with each dimer comprised of a large extracellular ligand-binding domain, a single-pass transmembrane domain, and a smaller cytoplasmic subunit (Notch intracellular domain, NICD) (2). Binding of Notch receptors to ligands of the Delta-Serrate-Lag2 (DSL) family triggers heterodimer dissociation, exposing the receptors to proteolytic cleavages; these result in release of the NICD, which translocates to the nucleus and activates transcription of downstream target genes (3,4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Ubiquitin is a conserved polypeptide unit that plays an important role in the ubiquitin-proteasome pathway. Ubiquitin can be covalently linked to many cellular proteins by the ubiquitination process, which targets proteins for degradation by the 26S proteasome. Three components are involved in the target protein-ubiquitin conjugation process. Ubiquitin is first activated by forming a thiolester complex with the activation component E1; the activated ubiquitin is subsequently transferred to the ubiquitin-carrier protein E2, then from E2 to ubiquitin ligase E3 for final delivery to the epsilon-NH2 of the target protein lysine residue (1-3). The ubiquitin-proteasome pathway has been implicated in a wide range of normal biological processes and in disease-related abnormalities. Several proteins such as IκB, p53, cdc25A, and Bcl-2 have been shown to be targets for the ubiquitin-proteasome process as part of regulation of cell cycle progression, differentiation, cell stress response, and apoptosis (4-7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse

Application Methods: Immunohistochemistry (Paraffin), Western Blotting

Background: Acetylation of the histone tail causes chromatin to adopt an "open" conformation, allowing increased accessibility of transcription factors to DNA. The identification of histone acetyltransferases (HATs) and their large multiprotein complexes has yielded important insights into how these enzymes regulate transcription (1,2). HAT complexes interact with sequence-specific activator proteins to target specific genes. In addition to histones, HATs can acetylate nonhistone proteins, suggesting multiple roles for these enzymes (3). In contrast, histone deacetylation promotes a "closed" chromatin conformation and typically leads to repression of gene activity (4). Mammalian histone deacetylases can be divided into three classes on the basis of their similarity to various yeast deacetylases (5). Class I proteins (HDACs 1, 2, 3, and 8) are related to the yeast Rpd3-like proteins, those in class II (HDACs 4, 5, 6, 7, 9, and 10) are related to yeast Hda1-like proteins, and class III proteins are related to the yeast protein Sir2. Inhibitors of HDAC activity are now being explored as potential therapeutic cancer agents (6,7).

$122
20 µl
$303
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Eukaryotic elongation factor 2 kinase (eEF2k) phosphorylates and inactivates eEF2, resulting in the inhibition of peptide-chain elongation (1). eEF2k is normally dependent on Ca2+ ions and calmodulin (2,3). It can be activated by PKA in response to elevated cAMP levels (4-6), which are generally increased in stress- or starvation-related conditions. eEF2k can also be regulated in response to a wide range of stimuli that promote cell growth and protein synthesis. This involves the phosphorylation of eEF2k by p90RSK and p70 S6 kinase at Ser366 or by SAPK4/p38delta at Ser359, leading to the inactivation of eEF2k (7,8), which facilitates the dephosphorylation of eEF2, and thus promotes translation.

$122
20 µl
$303
100 µl
$717
300 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Western Blotting

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).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Western Blotting

Background: The WNK [with no lysine (K)] family of serine/threonine kinases is characterized by having a cysteine in place of lysine in subdomain II of its kinase activation domain (1,2). The lysine necessary for phosphoryl transfer is located in an atypical position in the catalytic domain. Four WNK family members have been identified in humans (WNK1-4) and have been implicated in regulating ion permeability (3). Mutations in the WNK1 and WNK4 genes in humans cause pseudohypoaldosteronism type II (PHAII), an autosomal dominant disorder leading to hypertension, hyperkalemia, and renal tubular acidosis (4). WNK4 is specifically expressed in the kidney, whereas WNK1 has a wider distribution but is predominantly expressed in polarized epithelia (1-3). Heterozygous mutations in WNK1 in mice result in a significant decrease in blood pressure, while homozygous mutations are embryonic lethal (5). WNK1 is phosphorylated by Akt at Thr60 (6). In addition, WNK1 may be autophosphorylated at Ser382 in the activation loop, and this is thought to be required for its kinase activity (7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Miz-1 (Zbtb17) is a poxvirus and zinc finger (POZ) transcription factor with an amino-terminal BTB/POZ domain and 13 carboxy-terminal zinc finger domains. Miz-1 plays a key role in cell cycle control through activation of the cyclin-dependent kinase inhibitors p15, INK4B, and p21 Waf1/Cip1 (1-4). The transcriptional activity of Miz-1 is repressed through direct interaction with Myc (1-4). In the presence of DNA damage, Myc is recruited to the p21 Waf1/Cip1 promoter by Miz-1 and blocks p53-mediated induction of p21 Waf1/Cip1, ultimately resulting in p53-mediated apoptosis rather than cell cycle arrest (4). Miz-1 also plays a role during lymphocyte development. In developing B and T cells, Miz-1 represses suppressor of cytokine signaling 1 (SOCS1) expression, which enables signaling through the IL-7 receptor and upregulation of the pro-survival protein Bcl-2 (5,6).

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

Application Methods: Chromatin IP, Western Blotting

Background: Suppressor of Ty-16 (SPT16) and structure-specific recognition protein-1 (SSRP1) are subunits of the facilitates chromatin transcription (FACT) complex that is essential for transcription elongation (1,2). FACT facilitates RNA polymerase-dependent transcription of chromatin templates by destabilizing the nucleosomes within the open reading frames of active genes (3-5). FACT destabilizes the nucleosomes, which would otherwise act as barriers to RNA polymerase transcription activity, by disrupting histone-histone and histone-DNA contacts that lead to the eviction of the histone H2A-H2B dimer (2,3,6). FACT may also function as a histone chaperone to reassemble nucleosomes after RNA polymerase passage (7). In addition to transcription, FACT activity has been shown to have a role in DNA replication in yeast and in DNA repair by contributing to the activation of p53 by CK2 and by facilitating histone H2AX-H2B exchange upon DNA damage (8-10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Western Blotting

Background: The matrix metalloproteinase (MMP) family of proteases are a group of zinc-dependent enzymes that target extracellular proteins, including growth factors, cell surface receptors, adhesion molecules, and other proteases (1). Matrix metalloproteinases can be broadly categorized based on function and cellular localization, and include six distinct membrane-type (MT) metalloproteinases that share a transmembrane domain and short cytoplasmic tail (2). Membrane type-1 matrix metalloproteinase (MT1-MMP, MMP14) is involved in regulating development, angiogenesis, tissue remodeling, and tumor progression (3-6). MT1-MMP and other metalloproteinases promote tumor cell invasion by accumulating in specialized structures known as invadopodia, which remodel the ECM and allow tumor cells to breach the basement membrane (7). The abundance and presence of MT1-MMP at the cell surface is controlled by targeted endocytosis, which may be regulated by the MT1-MMP cytoplasmic domain (8). MT1-MMP protease activity can be further regulated through homodimer formation, autocatalytic processing, domain shedding and the interaction with inhibitory proteins. Activation of the MT1-MMP proenzyme results from cleavage of full-length MT1-MMP by furin in the trans-Golgi network, which removes the inhibitory propeptide domain (9). At the cell surface, MT1-MMP can be found in a protein complex with the soluble metalloproteinase MMP2 and the MMP inhibitor TIMP2. MT1-MMP mediated cleavage and activation of MMP2 generates the active MMP2 collagenase, which plays important roles in ECM remodeling and tumor invasion (10). MT1-MMP interacts with a large number of substrates in addition to MMP2, including interstitial collagens, adhesive glycoproteins (i.e. laminin), and cell surface receptors (11).