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Product listing: FE65 Antibody, UniProt ID O00213 #2877 to DNMT3B (E4I4O) Rabbit mAb (Mouse Specific), UniProt ID O88509 #48488

$260
100 µl
APPLICATIONS
REACTIVITY
Mouse, Rat

Application Methods: Western Blotting

Background: FE65, FE65L1 and FE65L2 are members of the FE65 protein family. FE65 is an adaptor protein with protein-protein interaction domains including a WW domain followed by two phosphotyrosine interaction domains (PID1 and PID2) (1). Amyloid beta precursor protein (APP) binds to PID2 and undergoes sequential cleavage. First alpha-/beta secretases cleave and release the ectodomain into the extracellular environment. Subsequent processing by the gamma-secretase complex results in the APP intracellular domain (AICD) and the beta-amyloid peptides. The latter A-beta fragments form the main components of amyloid plaques in patients with Alzheimer's disease (2). FE65 family members can regulate APP processing, resulting in elevated levels of A-beta (3). Double knock-out mice of FE65 and FE65L1 display a phenotype that occurs in animals lacking APP family members, supporting a functional interaction between FE65 and APP (4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: The Eph receptors are the largest known family of receptor tyrosine kinases (RTKs). They can be divided into two groups based on sequence similarity and on their preference for a subset of ligands. While EphA receptors bind to a glycosylphosphatidylinositol-anchored ephrin A ligand, EphB receptors bind to ephrin B proteins that have a transmembrane and cytoplasmic domain (1,2). Research studies have shown that Eph receptors and ligands may be involved in many diseases including cancer (3). Both ephrin A and B ligands have dual functions. As RTK ligands, ephrins stimulate the kinase activity of Eph receptors and activate signaling pathways in receptor-expressing cells. The ephrin extracellular domain is sufficient for this function as long as it is clustered (4). The second function of ephrins has been described as "reverse signaling", whereby the cytoplasmic domain becomes tyrosine phosphorylated, allowing interactions with other proteins that may activate signaling pathways in the ligand-expressing cells (5).The EphA7 receptor preferentially binds ephrin-A5 as a ligand. This ligand-receptor interaction stimulates EphA7 signaling and induces apoptotic cell death through TNFR1 and caspase-8 pathway (6,7). EphA7 plays a critical role in organ development during neural tube closure, cortical dendritic development and spine maturation as well as urine tract insertion (8-10). Secreted EphA7 has been shown to promote somatic cell reprogramming through ERK activity reduction (11). Silencing of the secreted form of EphA7 is associated with germinal center B cell lymhomas. The secreted form of EphA7 has been proposed as a soluble tumor suppresor in lymphoma (12-14).

$262
3 nmol
300 µl
SignalSilence® SP1 siRNA I from Cell Signaling Technology (CST) allows the researcher to specifically inhibit SP1 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: Specificity protein 1 (SP1) is a ubiquitously expressed transcription factor belonging to the family of C2H2-type zinc finger containing DNA-binding proteins. SP1 binds GC-rich motifs with high affinity and regulates the expression of numerous mammalian genes (1,2). It interacts with many other transcription factors, such as c-Myc, EGR1, and Stat1, and with basal transcription machinery components. SP1 interacts with chromatin-modifying factors, such as histone deacetylases (HDACs) and p300 in chromatin remodeling. Transcriptional activity and stability of SP1 are regulated by post-translational modification, including phosphorylation, acetylation, ubiquitination, and glycosylation (3). Glycosylation of SP1 following insulin treatment leads to increased nuclear localization, while glucagon treatment increases cytoplasmic SP1 levels (4-6). Investigators have found high levels of SP1 in patients with Alzheimer's disease (7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: During translation, eIF4E binds to the 5' cap structure of mRNA and helps mRNA bind to the ribosome. There are several factors that associate with eIF4E. One of these factors is eIF4E-Transporter (4E-T) (1). 4E-T has an eIF4E binding site, a nuclear localization signal and two nuclear export signals (1). Studies demonstrate that 4E-T functions as a nucleocytoplasmic shuttling protein mediating the import of eIF4E into the nucleus (1). Recent findings indicate that 4E-T, along with eIF4E, is concentrated in the processing bodies (P-bodies) in the cytoplasm (2). Furthermore, 4E-T decreases mRNA stability (2).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Flow Cytometry

Background: Cytotoxic T-lymphocyte protein 4 (CTLA-4, CD152) is an Ig superfamily member that negatively regulates early T cell activation (1-4). The CTLA-4 protein is primarily expressed on T cells, including CD8+ cytotoxic T cells, CD4+ helper T cells, and CD4+/FoxP3+ regulatory T cells (1,2). CTLA-4 protein competes with CD28 for B7.1 (CD80) and B7.2 (CD86) binding at the cell surface, which results in the down regulation of T cell activity (5). The activation of SHP-2 and PP2A downstream of CTLA-4 attenuates TCR signaling (6). Research studies indicate that CTLA4 knockout mice display lymphoproliferative disorders leading to early death, confirming the role of CTLA-4 as a negative regulator of T cells (7). Mutations in the corresponding CTLA4 gene are associated with multiple disorders, including insulin-dependent diabetes mellitus, Graves disease, Hashimoto thyroiditis, celiac disease, systemic lupus erythematosus, and type V autoimmune lymphoproliferative syndrome (8,9). Additional studies demonstrate that CTLA-4 blockade is an effective strategy for tumor immunotherapy (10-12).

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

Application Methods: Western Blotting

Background: Numb contains an amino-terminal phosphotyrosine-binding (PTB) domain and carboxy-terminal endocytic binding motifs for α-adaptin and EH (Eps15 homology) domain-containing proteins, indicating a role in endocytosis (1,2). There are four mammalian Numb splicing isoforms that are differentially expressed and may have distinct functions (3-5). Numb acts as a negative regulator of Notch signaling by promoting ubiquitination and degradation of Notch (6). The protein is asymmetrically segregated into one daughter cell during cell division, producing two daughter cells with different responses to Notch signaling and different cell fates (7,8). The localization of Numb can also be regulated by G-protein coupled receptor (GPCR) and PKC signaling (9).

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

Application Methods: Western Blotting

Background: Leucine-rich repeat and sterile alpha motif-containing protein 1 (LRSAM1, hTAL1) is a multi-domain-containing E3 ubiquitin-ligase involved in the regulation of cell adhesion. The LSRAM1 protein contains amino-terminal leucine-rich repeats (LRR), an ezrin-radixin-moesin (ERM) domain, a coiled-coil region, a sterile alpha motif (SAM) domain, and a carboxy-terminal RING finger domain. Research studies demonstrate that LRSAM1 participates in the endosomal sorting of proteins by regulating the ubiquitination of Tsg101, a component of the ESCRT-I endosomal sorting complex (1). LSRAM1 ubiquitin ligase activity plays a critical role in promoting the ubiquitin-dependent autophagic clearance of pathogenic bacteria (2). Mutations in the corresponding LRSAM1 gene can contribute to a form of Charcot-Marie-Tooth (CMT2P) disease that is characterized by peripheral nervous system axonal neuropathy (3,4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: PICK1, or Protein interacting with C-kinase 1, is a cytosolic adaptor protein composed of an N-terminus PDZ domain and a C-terminus BAR domain that allow protein and membrane interactions, respectively (1,2). PICK1 regulates endosomal trafficking and surface expression of AMPA receptors and is therefore involved in synaptic plasticity (3). PICK1 is a negative regulator of Arp2/3-dependent actin polymerization and also for the development of neuronal architecture (4). Finally, increasing evidence indicates that PICK1 expression is upregulated in a number cancers (5), and that PICK1 interacts with proteins involved in the promotion of tumorigenesis such as Ephrin receptors, Coxsackie-adenovirus receptor (CAR), and ErbB2/Her2 (6,7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: The electroneutral cation-chloride-coupled co-transporter (SLC12) gene family comprises bumetanide-sensitive Na+/K+/Cl- (NKCC), thiazide-sensitive Na+/Cl-, and K+/Cl- (KCC) co-transporters. SLC12A1/NKCC2 and SLC12A2/NKCC1 regulate cell volume and maintain cellular homeostasis in response to osmotic and oxidative stress (1). The broadly expressed NKCC1 is thought to play roles in fluid secretion (i.e. salivary gland function), salt balance (i.e. maintenance of renin and aldosterone levels), and neuronal development and signaling (2-7). During neuronal development, NKCC1 and KCC2 maintain a fine balance between chloride influx (NKCC1) and efflux (KCC2), which regulates γ-aminobutyric acid (GABA)-mediated neurotransmission (3). Increased NKCC1 expression in immature neurons maintains high intracellular chloride levels that result in inhibitory GABAergic signaling; KCC2 maintains low intracellular chloride levels and excitatory GABAergic responses in mature neurons (4,5,8). Deletion of NKCC1 impairs NGF-mediated neurite outgrowth in PC-12D cells while inhibition of NKCC1 with bumetanide inhibits re-growth of axotomized dorsal root ganglion cells (6,7). Defective chloride homeostasis in neurons is linked to seizure disorders that are ameliorated by butemanide treatment, indicating that abnormal NKCC1 and NKCC2 expression or signaling may play a role in neonatal and adult seizures (9-12). NKCC1 is found as a homodimer or within heterooligomers with other SLC12 family members. This transport protein associates with a number of oxidative- and osmotic-responsive kinases that bind, phosphorylate, and activate NKCC1 co-transporter activity (13-16). In response to decreased intracellular chloride concentrations, Ste20-related proline-alanine-rich kinase (SPAK) phosphorylates NKCC1 to increase co-transporter activity and promote chloride influx (16-19). Oxidative stress response kinase 1 (OSR1) also phosphorylates and activates NKCC1 in response to oxidative stress (14).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Mannose-binding lectin-1 (LMAN1, ERGIC-53) is a type I transmembrane lectin protein localized to the intermediate compartment between the endoplasmic reticulum and the Golgi body (ERGIC) (1). Interaction between the LMAN1 protein and MCFD2 forms an ERGIC cargo receptor that delivers proteins from the ER to the Golgi body (2,3). The LMAN1 protein contains an amino-terminal carbohydrate recognition domain (CRD) that binds target glycoproteins, a membrane proximal oligomerization domain required for cargo transport, a single transmembrane segment, and short cytoplasmic tail (3-5). LMAN1 functions as a cargo receptor responsible for transport of glycoproteins from the ER to ERGIC and Golgi body. Target proteins include coagulation factors V and VIII, cathepsin C, cathepsin Z, and α1-antitrypsin (6-8). Mutations in the corresponding LMAN1 gene can result in combined factors FV and FVIII deficiency, an autosomal recessive disorder characterized by spontaneous bleeding (9). Inactivating frameshift mutations in LMAN1 are found at high frequency in colorectal tumors with microsatellite instability and may contribute to tumorigenesis (10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Leucine-rich repeat and immunoglobulin domain-containing protein (LINGO-1) is a potent negative modulator of neuronal processes including neuronal survival, axonal integrity, oligodendrocyte differentiation, and myelination (1-5). LINGO-1, Nogo receptor (NgR), and p75 neurotrophin receptor (p75NTR), or TNF receptor orphan Y (TROY) form a tripartite receptor complex, which activates RhoA/ROCK signaling and is responsible for the inhibition effect of myelin- associated factors (6,7). LINGO-1 is abundantly expressed in the brain and is implicated in various neurodegenerative disorders such as Essential tremor, multiple sclerosis and Parkinson’s disease (8-11). Recently, LINGO-1 was reported to bind directly to amyloid precursor protein (APP), promoting its degradation through lysosomal proteolysis (12). This research study implicated that Lingo-1 plays a critical role in the pathophysiology of Alzheimer's disease.

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Glucose homeostasis is regulated by hormones and cellular energy status. Elevations of blood glucose during feeding stimulate insulin release from pancreatic β-cells through a glucose sensing pathway. Feeding also stimulates release of gut hormones such as glucagon-like peptide-1 (GLP-1), which further induces insulin release, inhibits glucagon release and promotes β-cell viability. CREB-dependent transcription likely plays a role in both glucose sensing and GLP-1 signaling (1). The protein CRTC2 (CREB-regulated transcription coactivator 2)/TORC2 (transducer of regulated CREB activity 2) functions as a CREB co-activator (2,3) and is implicated in mediating the effects of these two pathways (4). In quiescent cells, CRTC2/TORC2 is phosphorylated at Ser171 and becomes sequestered in the cytoplasm via an interaction with 14-3-3 proteins. Glucose and gut hormones lead to the dephosphorylation of CRTC2/TORC2 and its dissociation from 14-3-3 proteins. Dephosphorylated CRTC2/TORC2 enters the nucleus to promote CREB-dependent transcription. CRTC2/TORC2 plays a key role in the regulation of hepatic gluconeogenic gene transcription in response to hormonal and energy signals during fasting (5).CRTC2/TORC2-related proteins CRTC1/TORC1 and CRTC3/TORC3 also act as CREB co-activators (2,3). CRTC1/TORC1, CRTC2/TORC2 and CRTC3/TORC3 associate with the HTLV Tax protein to promote Tax-dependent transcription of HTLV-1 long terminal repeats (6,7). CRTC1/TORC1 is highly phosphorylated at Ser151 in mouse hypothalamic cells under basal conditions (8). When these cells are exposed to cAMP or a calcium activator, CRTC1/TORC1 is dephosphorylated and translocates into the nucleus (8). CRTC1/TORC1 is essential for energy balance and fertility (8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

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

Background: Complexins are small soluble proteins composed of a central α-helical-structured domain surrounded by amino- and carboxy-terminal unstructured domains (1). These cytosolic proteins bind to t-SNAREs with low affinity and to assembled SNARE complexes with high affinity (1,2). Two isoforms, complexin-1 and complexin-2, are expressed in neuronal cells (3) where they regulate evoked and spontaneous exocytosis (4,5). Altered complexin expression resulting from RNAi-mediated knockdown (6) or gene invalidation (7) leads to alteration in spontaneous fusion events and neurotransmitter release, which reflects functions at both inhibitory and stimulatory synapses.

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

Application Methods: Immunoprecipitation, Western Blotting

Background: 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 thioester complex with the ubiquitin-activating enzyme (E1). The activated ubiquitin is subsequently transferred to the ubiquitin-carrier protein E2, and then from E2 to ubiquitin ligase E3 for final delivery to the ε-amino group of the target protein lysine residue (1-3).Ubiquitin-activating enzyme E1-like protein 2/Ubiquitin-like modifier-activating enzyme 6 (UBE1L2/UBA6) is ubiquitously expressed in human tissues and functions as an E1 enzyme related to UBE1/UBA1 (40% identity at the protein level). UBE1L2/UBA6 activates both ubiquitin and the ubiquitin-like protein FAT10 through a similar ATP dependent mechanism (4-6). Like other E1 protein family members, UBE1L2/UBA6 contains a conserved ATP-binding adenylation domain and an active site cysteine residue that are critical for enzymatic function (4,5). Research studies have demonstrated that UBE1L2/UBA6 expression is essential during the early stages of embryogenesis in mice (4). Furthermore, loss of neuronal UBE1L2/UBA6 expression promotes significant defects in neuronal structure and function, which contributes to a reduction in body weight and decreased postnatal viability (7).

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

Application Methods: Western Blotting

Background: The 26S proteasome is a highly abundant proteolytic complex involved in the degradation of ubiquitinated substrate proteins. It consists largely of two sub-complexes, the 20S catalytic core particle (CP) and the 19S/PA700 regulatory particle (RP) that can cap either end of the CP. The CP consists of two stacked heteroheptameric β-rings (β1-7) that contain three catalytic β-subunits and are flanked on either side by two heteroheptameric α-rings (α1-7). The RP includes a base and a lid, each having multiple subunits. The base, in part, is composed of a heterohexameric ring of ATPase subunits belonging to the AAA (ATPases Associated with diverse cellular Activities) family. The ATPase subunits function to unfold the substrate and open the gate formed by the α-subunits, thus exposing the unfolded substrate to the catalytic β-subunits. The lid consists of ubiquitin receptors and DUBs that function in recruitment of ubiquitinated substrates and modification of ubiquitin chain topology (1,2). Other modulators of proteasome activity, such as PA28/11S REG, can also bind to the end of the 20S CP and activate it (1,2).

$260
100 µl
APPLICATIONS
REACTIVITY
Mouse, Rat

Application Methods: Immunofluorescence (Frozen), Immunofluorescence (Immunocytochemistry)

Background: Anion exchange protein 1 (AE1), also named solute carrier family 4 member 1 (SLC4A1), is an anion transporter that mediates chloride-bicarbonate exchange in the kidney and regulates normal acidification of the urine (1,2). A different isoform of AE1 is a major integral membrane structure protein of erythrocytes, where it plays a critical role in the removal of carbon dioxide from tissues (3). In addition, AE1 is required for normal flexibility and stability of the erythrocyte membrane. Mutations in SLC4A1 can lead to hereditary spherocytosis, ovalocytosis, and distal renal tubular-acidosis (4-7). Other mutations that do not cause disease became novel blood group antigens, which are part of the Diego blood group system (8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Western Blotting

Background: Mitotic control is important for normal growth, development, and maintenance of all eukaryotic cells. Research studies have demonstrated that inappropriate control of mitosis can lead to genomic instability and cancer (reviewed in 1,2). A regulator of mitosis, Greatwall kinase (Gwl), was first identified in Drosophila melanogaster (3). Subsequent studies showed that, based on sequence homology and function, microtubule-associated serine/threonine kinase-like (MASTL) is the human ortholog of Gwl (4). Regulation of MASTL/Gwl activation has been shown to be critical for the correct timing of mitosis. Research studies have shown that Gwl is activated by hyperphosphorylation (5). The phosphorylation of human Gwl at Thr194 and Thr207 by active cyclin B1-cdc2 leads to possible autophosphorylation at Ser875 (Ser883 in Xenopus), which stabilizes the kinase. Activated Gwl phosphorylates α-Endosulfine (ENSA) and cAMP-regulated phosphoprotein 19 (ARPP19) at Ser67 and Ser62, respectively. Phosphorylated ENSA and ARPP19 inhibit the activity of the B55 subunit-associated form of protein phosphatase 2A (PP2A-B55), allowing for complete phosphorylation of mitotic substrates by cyclin B1-cdc2 and mitotic entry. When Gwl is inactivated, PP2A-B55 reactivates, which leads to dephosphorylation of cyclin B1-cdc2 and mitotic exit (5,6, reviewed in 7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: MEX3C is an RNA-binding E3 ubiquitin ligase implicated in a diverse set of biological functions.Along with PIGN and ZNF516, MEX3C has been identified as a suppressor of chromosome instability (CIN), which drives intratumor heterogeneity and has been associated with poor prognosis in colon cancer. Silencing of the Mex3c gene induces chromosome instability through replication stress/impaired replication fork progression (1).In mice, absence of the Mex3c gene causes growth retardation and reduced insulin-like growth factor 1 (IGF1) expression (2). Researchers have shown that murine MEX3C plays a role in controlling energy expenditure, physical activity and degree of adiposity (3,4). In the immune system, MEX3C is involved in post-transcriptional regulation of HLA-A2 (5), and plays a role in eliciting antiviral response (6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Dicer is a member of the RNase III family that specifically cleaves double-stranded RNAs to generate microRNAs (miRNAs) (1). After long primary transcript pri-miRNAs are processed to stem-looped pre-miRNAs by Drosha (2), pre-miRNAs are transported to the cytoplasm and further processed by Dicer to produce 22-nucleotide mature miRNAs (3). The mature miRNA then becomes a part of the RNA-Induced Silencing Complex (RISC) and can bind to the 3' UTR of the target mRNA (3).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: Tripeptidyl-peptidase 2 (TPP2) is a well-conserved subtilisin-like amino peptidase that is expressed predominantly in the cytoplasmic compartment (1,2). The amino-terminal region of TPP2 harbors a catalytic triad that is characteristic of serine proteases and allows for TPP2 cleavage of tripeptides from the free amino terminus of oligopeptide substrates (3). TPP2 is a large (>5MDa) homooligomeric protease in which proteolytic activity is regulated by subunit oligomerization (4,5). While TPP2 plays a general role in amino acid homeostasis, research studies demonstrate that TPP2 is involved in MHC class I antigen presentation (6,7) and DNA-damage repair (8). TPP2 activity is required for the survival of Burkitt's lymphoma cells, suggesting a possible role for TPP2 in oncogenesis (9). Additional research studies show that TPP2 proteolytic activity is important for regulating lysosome abundance and glycolytic metabolism and that TPP2 deficiency leads to defects in adaptive immunity, innate immunity, and nervous system development (10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: DNA damage resulting from genotoxic stress activates cellular checkpoints that prevent or delay cell division until either damaged DNA is repaired or the cell follows an apoptotic pathway. The Rad9 homolog A (Rad9A, Rad9) protein is part of a checkpoint protein complex that acts as an early sensor of DNA damage. Together with the Hus1 and Rad1 checkpoint proteins, Rad9 forms a heterotrimeric 9-1-1 complex with a ring structure similar to the processivity factor PCNA. The 9-1-1 complex induces multiple signaling pathways, including the ATM and ATR-activated DNA repair pathways (1,2). A functional 9-1-1 complex is required for ATR-dependent S phase checkpoint signaling (3).The 9-1-1 complex interacts with DNA topoisomerase 2-binding protein 1 (TopBP1) in response to DNA damage, activating ATR and causing signal amplification through further recruitment of TopBP1 (4). The 9-1-1 complex interacts with DNA mismatch repair proteins MSH2, MSH3, and MSH6 to play a role in mismatch repair (5). During an error-free DNA damage tolerance process, the 9-1-1 complex cooperates with polyubiquitinated PCNA and Exo1 nuclease to support switching of the replicative polymerase to the undamaged template (6).Research studies indicate that the two Rad9 paralogues (Rad9A and Rad9B) can both functionally complement one another and display distinct biological functions.Specifically, Rad9B senses nucleolar stress and causes a delay in the cell cycle at G1/S phase (7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Class 3 secreted semaphorin (Sema3A) is a chemorepellent that acts upon a wide variety of axons. As such, it induces a dramatic redistribution and depolymerization of actin filaments that results in growth cone collapse. Plexins are single membrane-spanning signaling proteins encompassing Plexin A1, A2, A3, and A4. Plexins form a complex with neuropilin-1 and -2 and the cell adhesion protein L1 to form a functional semaphorin receptor (1,2). The GTPase Rnd1 binds to the cytoplasmic domain of Plexin A1 to trigger cytoskeletal collapse. In contrast, the GTPase RhoD blocks Rnd1-mediated Plexin A1 activation and repulsion of sympathetic axons by Sema3A (3).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: p62Dok (Dok-1) is a major tyrosine-phosphorylated, GAP-associated, 60 kDa protein present within the cells transformed by different tyrosine kinases (1). p62Dok contains an amino-terminal pleckstrin homology domain potentially involved in phospholipid interaction and membrane targeting, a central putative phospho-tyrosine binding domain for interacting with tyrosine-phosphorylated proteins. There are numerous tyrosines in its carboxy-terminal region that are potential targets for tyrosine kinases. If phosphorylated, these tyrosines could serve as docking sites for proteins that contain an SH2 domain (2). Overexpression of p62Dok has been shown to inhibit Ras activity in human embryonic kidney 293 cells and B cell antigen receptor-mediated c-Fos promoter activation in an immature B cell line (3), suggesting that p62Dok may play a negative role in Ras signaling. Moreover, p62Dok overexpression may also inhibit insulin-stimulated Akt activation (4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Secreted Frizzled-related proteins (SFRPs) display homology and structural similarity to the extracellular cysteine-rich Wnt-binding domain of the G protein-coupled receptor Frizzled (1,2). To date, five distinct SFRPs (SFRP1 to 5) have been found in mammalian cells. These secreted proteins typically act as antagonists to Wnt signaling by directly binding and inhibiting Wnt proteins, or by binding Frizzled to block Wnt protein interaction with the receptor (3). The various SFRPs bind and regulate Wnt proteins differentially; these proteins also display distinct expression patterns as they play important roles in regulating development (4-7). SFRP proteins appear to act as tumor suppressors, with loss of expression or function correlating with many invasive forms of cancer. Deletion of the corresponding SFRP1 gene and promoter hypermethylation leading to gene silencing has been reported in a number of cancers. Abnormal expression of SRFP1 and other Wnt signaling proteins is associated with some cases of retinitis pigmentosa (reviewed in 8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse

Application Methods: Immunoprecipitation, Western Blotting

Background: CIN85 was independently identified as Cbl-interacting protein of 85 kDa (1), Ruk (regulator of ubiquitous kinase) (2), SETA (SH3 domain-containing gene expressed in tumorigenic astrocytes) (3), and SH3KBP1 (SH3 domain kinase binding protein 1) (4). The genes encoding these proteins were isolated from either human (CIN85), rat (Ruk and SETA), or mouse (SH3KBP1) sources and share between 92% and 97% sequence identity, suggesting that they represent homologues of one gene. Differential promoter usage and alternative splicing is thought to occur in a tissue specific and developmentally regulated manner to generate a complex expression pattern of various transcripts and encoded protein isoforms (5). The main isoform in humans, CIN85, contains three N-terminal SH3 domains, a proline-rich region harboring several P-X-X-P motifs that provide recognition sites for SH3 domain-containing proteins, a PEST sequence implicated in CIN85 degradation, and a C-terminal coiled-coil region for oligomerization (1,2,5,6). The other molecular variants of CIN85 are shorter, N-terminally truncated proteins lacking one, two, or all three of the SH3 domains (1,5,6-8). Proteomic screens suggest that CIN85 is phosphorylated at multiple sites and the role of phosphorylation of some of these sites in regulation of intra- and intermolecular interactions of CIN85 cannot be excluded. CIN85 belongs to the CD2AP/CMS family of adaptor proteins and has been shown to interact with signaling molecules such as c-Cbl, Cbl-b, BLNK, p85/PI3K, GRB2, p130 Cas, and endophilins to coordinate the activity of multiple signaling cascades. Indeed, a growing body of evidence suggests that CIN85 is required for the regulation of a variety of cellular processes including vesicle-mediated transport (9-12), signal transduction (13,14), and cytoskeleton remodelling (15).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Phosphatidylinositol lipids and phosphoinositides are important second messengers, their generation controlling many cellular events. Intracellular levels of these molecules are regulated by phosphoinositide kinases and phosphatases. One of the best characterized lipid kinases is phosphoinositide 3-kinase (PI3K), which is responsible for phosphorylation on the D-3 position of the inositide head group (1). This action of PI3K catalyzes the production of phosphatidylinositol-3,4,5-triphosphate by phosphorylating phosphatidylinositol (PI), phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP2). Growth factors and hormones trigger this phosphorylation event, which in turn coordinates cell growth, cell cycle entry, cell migration, and cell survival (1). PTEN, the well characterized partnering phosphatase, reverses this process by removing the phosphate from PI(3,4,5)P3 at the D-3 position to generate PI(4,5)P2 (1,2). Dephosphorylation on the D-5 position to generate PI(3,4)P2 occurs through the action of SHIP1 or SHIP2 (3), and dephosphorylation on the D-4 position to generate PI(3)P can occur through the action of inositol polyphosphate 4-phosphatase isoenzymes type I (INPP4a) and type II (INPP4b) (4,5). While INPP4a has been implicated in neuronal survival and megakaryocyte lineage determination (6,7), less is understood about INPP4b. It has been shown that two splice variants of INPP4b occur in mice, each showing distinct tissue distribution and subcellular localization (5,8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Cripto, also known as teratocarcinoma derived growth factor 1 (TDGF-1), belongs to the EGF-CFC family of proteins. Members of this family are characterized by an N-terminal signal peptide, a conserved cysteine rich domain (CFC motif), and a short hydrophobic carboxy-terminal tail that contains GPI cleavage and attachment sites. The GPI moiety anchors Cripto and family members to the extracellular plasma membrane (1). An O-linked fucosylation site within the EGF-like motif is required for Cripto and related family members to perform their function as co-receptors for TGF-β-related ligands such as Nodal and Vg1/GDF1 (2,3). Soluble forms of Cripto can be produced - these contain intact EGF and CFC domains, and are thought to have paracrine activities, as opposed to the autocrine activity of Cripto functioning as a coreceptor (4). Understanding of this paracrine activity is not complete, but it is proposed that Cripto may act as co-ligand for Nodal (3).Cripto is an important modulator of embryogenesis and oncogenesis (4). It is highly expressed in early embryos, and in embryonic stem (ES) cells where it is involved in cardiomyocytic differentiation and acts as a negative regulator of neurogenesis (5-7). Transient activation of Cripto is essential for the capacity of stem cell self-renewal and pluripotency in ES cells, and in some adult derived stem cells (8). Signaling through Cripto can also stimulate other activities that promote tumorigenesis such as stimulation of proliferation, cell motility, invasion, angiogenesis and epithelial-mesenchymal transition (EMT) (9-11). Cripto is highly expressed in a broad range of tumors, where it acts as a potent oncogene.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Immunoprecipitation, Western Blotting

Background: PZR (Protein zero related) is an immunoglobulin superfamily protein that specifically binds the tyrosine phosphatase SHP-2 through its intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs) (1,2). PZR is phosphorylated by c-Src, c-Fyn, c-Lyn, Csk, and c-Abl (3). PP1, a Src family kinase inhibitor, inhibits PZR phosphorylation (4,5). There are three alternatively spliced isoforms, designated as PZR, PZRa, and PZRb; both PZRa and PZRb lack ITIMs (6,7). PZR is the main receptor of ConA and has an important role in cell signaling via c-Src (4). PZR is expressed in many cell types and is localized to cell contacts and intracellular granules in BAECs and mesothelioma (REN) cells. PZR has been implicated as a cell adhesion protein that may be involved in SHP-2-dependent signaling at interendothelial cell contacts (3). Hypertyrosine phosphorylation of PZR was observed during embryogenesis in a mouse model of Noonan syndrome (8).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: The serum response factor (SRF) is a ubiquitous protein that modulates transcription of genes containing serum response elements (SRE) at their promoters. SRF regulates cellular processes such as cell proliferation and cytoskeletal signaling in conjunction with a variety of cofactors (1-3).Suppressor of cancer cell invasion (SCAI) is a highly conserved transcriptional cofactor that inhibits the activity of myocardin-related transcription factor (MRTF) family members MAL (MRTF-A), myocardin and OTT-MAL (4,5). SCAI controls the expression of integrin β1 and regulates cell migration and invasion in vitro (4). SCAI has also been shown to play a role in transcriptional regulation in neurons by regulating dendritic morphology through inhibition of the megakaryoblastic leukemia (MKL) family of transcription cofactors (6). Research studies have implicated SCAI in the regulation of the epithelial-to-mesenchymal transition (EMT) as well as in renal fibrosis (7).

$260
100 µl
APPLICATIONS
REACTIVITY
Mouse

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

Background: Methylation of DNA at cytosine residues in mammalian cells is a heritable, epigenetic modification that is critical for proper regulation of gene expression, genomic imprinting and development (1,2). Three families of mammalian DNA methyltransferases have been identified: DNMT1, DNMT2 and DNMT3 (1,2). DNMT1 is constitutively expressed in proliferating cells and functions as a maintenance methyltransferase, transferring proper methylation patterns to newly synthesized DNA during replication. DNMT3A and DNMT3B are strongly expressed in embryonic stem cells with reduced expression in adult somatic tissues. DNMT3A and DNMT3B function as de novo methyltransferases that methylate previously unmethylated regions of DNA. DNMT2 is expressed at low levels in adult somatic tissues and its inactivation affects neither de novo nor maintenance DNA methylation. DNMT1, DNMT3A and DNMT3B together form a protein complex that interacts with histone deacetylases (HDAC1, HDAC2, Sin3A), transcriptional repressor proteins (RB, TAZ-1) and heterochromatin proteins (HP1, SUV39H1), to maintain proper levels of DNA methylation and facilitate gene silencing (3-8). Improper DNA methylation contributes to diseased states such as cancer (1,2). Hypermethylation of promoter CpG islands within tumor suppressor genes correlates with gene silencing and the development of cancer. In addition, hypomethylation of bulk genomic DNA correlates with and may contribute to the onset of cancer. DNMT1, DNMT3A and DNMT3B are over-expressed in many cancers, including acute and chronic myelogenous leukemias, in addition to colon, breast and stomach carcinomas (9-12).