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Product listing: PSD95 (D74D3) XP® Rabbit mAb, UniProt ID P78352 #3409 to PRMT4/CARM1 (C31G9) Rabbit mAb, UniProt ID Q86X55 #3379

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

Application Methods: Immunohistochemistry (Paraffin), Western Blotting

Background: Postsynaptic Density protein 95 (PSD95) is a member of the membrane-associated guanylate kinase (MAGUK) family of proteins. These family members consist of an amino-terminal variable segment followed by three PDZ domains, a SH3 domain, and an inactive guanylate kinase (GK) domain. PSD95 is a scaffolding protein involved in the assembly and function of the postsynaptic density complex (1-2). PSD95 participates in synaptic targeting of AMPA receptors through an indirect manner involving Stargazin and related transmembrane AMPA receptor regulatory proteins (TARPs) (3). It is implicated in experience-dependent plasticity and plays an indispensable role in learning (4). Mutations in PSD95 are associated with autism (5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Vascular endothelial growth factor receptor 3 (VEGFR3) is a 195 kDa membrane receptor tyrosine kinase. VEGF receptors are characterized by the presence of seven extracellular immunoglobulin (Ig)-like domains followed by a membrane-spanning domain and a conserved intracellular tyrosine kinase domain (1). VEGF receptor 3 expression is largely restricted to adult lymphatic endothelium and is thought to control lymphangiogenesis (1,2). Binding of VEGF-C/VEGF-D to VEGFR3 results in transphosphorylation of tyrosine residues in its intracellular domain, recruitment of signaling molecules and activation of ERK1/2 and Akt signaling cascades (1,3).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: Insulin receptor substrate 1 (IRS-1) is one of the major substrates of the insulin receptor kinase (1). IRS-1 contains multiple tyrosine phosphorylation motifs that serve as docking sites for SH2-domain containing proteins that mediate the metabolic and growth-promoting functions of insulin (2-4). IRS-1 also contains over 30 potential serine/threonine phosphorylation sites. Ser307 of IRS-1 is phosphorylated by JNK (5) and IKK (6) while Ser789 is phosphorylated by SIK-2, a member of the AMPK family (7). The PKC and mTOR pathways mediate phosphorylation of IRS-1 at Ser612 and Ser636/639, respectively (8,9). Phosphorylation of IRS-1 at Ser1101 is mediated by PKCθ and results in an inhibition of insulin signaling in the cell, suggesting a potential mechanism for insulin resistance in some models of obesity (10).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Macrophage-colony stimulating factor (M-CSF, CSF-1) receptor is an integral membrane tyrosine kinase encoded by the c-fms proto-oncogene. M-CSF receptor is expressed in monocytes (macrophages and their progenitors) and drives growth and development of this blood cell lineage. (1-3). Binding of M-CSF to its receptor induces receptor dimerization, activation, and autophosphorylation of cytoplasmic tyrosine residues used as docking sites for SH2-containing signaling proteins (4). There are at least five major tyrosine autophosphorylation sites. Tyr723 (Tyr721 in mouse) is located in the kinase insert (KI) region. Phosphorylated Tyr723 binds the p85 subunit of PI3 kinase as well as PLCγ2 (5). Phosphorylation of Tyr809 provides a docking site for Shc (5). Overactivation of this receptor can lead to a malignant phenotype in various cell systems (6). The activated M-CSF receptor has been shown to be a predictor of poor outcome in advanced epithelial ovarian carcinoma (7) and breast cancer (8).

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

Application Methods: Western Blotting

Background: Nonmuscle myosin is an actin-based motor protein essential to cell motility, cell division, migration, adhesion, and polarity. The holoenzyme consists of two identical heavy chains and two sets of light chains. The light chains (MLCs) regulate myosin II activity and stability. The heavy chains (NMHCs) are encoded by three genes, MYH9, MYH10, and MYH14, which generate three different nonmuscle myosin II isoforms, IIa, IIb, and IIc, respectively (reviewed in 1). While all three isoforms perform the same enzymatic tasks, binding to and contracting actin filaments coupled to ATP hydrolysis, their cellular functions do not appear to be redundant and they have different subcellular distributions (2-5). The carboxy-terminal tail domain of myosin II is important in isoform-specific subcellular localization (6). Research studies have shown that phosphorylation of myosin IIa at Ser1943 contributes to the regulation of breast cancer cell migration (7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

Background: Nonmuscle myosin is an actin-based motor protein essential to cell motility, cell division, migration, adhesion, and polarity. The holoenzyme consists of two identical heavy chains and two sets of light chains. The light chains (MLCs) regulate myosin II activity and stability. The heavy chains (NMHCs) are encoded by three genes, MYH9, MYH10, and MYH14, which generate three different nonmuscle myosin II isoforms, IIa, IIb, and IIc, respectively (reviewed in 1). While all three isoforms perform the same enzymatic tasks, binding to and contracting actin filaments coupled to ATP hydrolysis, their cellular functions do not appear to be redundant and they have different subcellular distributions (2-5). The carboxy-terminal tail domain of myosin II is important in isoform-specific subcellular localization (6). Research studies have shown that phosphorylation of myosin IIa at Ser1943 contributes to the regulation of breast cancer cell migration (7).

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

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

Background: Nonmuscle myosin is an actin-based motor protein essential to cell motility, cell division, migration, adhesion, and polarity. The holoenzyme consists of two identical heavy chains and two sets of light chains. The light chains (MLCs) regulate myosin II activity and stability. The heavy chains (NMHCs) are encoded by three genes, MYH9, MYH10, and MYH14, which generate three different nonmuscle myosin II isoforms, IIa, IIb, and IIc, respectively (reviewed in 1). While all three isoforms perform the same enzymatic tasks, binding to and contracting actin filaments coupled to ATP hydrolysis, their cellular functions do not appear to be redundant and they have different subcellular distributions (2-5). The carboxy-terminal tail domain of myosin II is important in isoform-specific subcellular localization (6). Research studies have shown that phosphorylation of myosin IIa at Ser1943 contributes to the regulation of breast cancer cell migration (7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

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

Background: Myosin Va is a molecular motor protein involved in the transport of organelles, vesicles and other cellular cargo along actin filaments (reviewed in 1). The molecule consists of two identical heavy chains, which dimerize via helical domains in a coiled coil structure. The amino-terminal motor domains of the heavy chains contain both the ATPase and the actin-binding activities of myosin Va. The globular tail domains act in a regulatory capacity, binding the myosin Va cargo (2) or inhibiting motor activity by binding the head domains and preventing ATP consumption (3). Mutation of the murine dilute gene, which encodes myosin Va, causes defects in coat pigmentation as well as severe neurological defects (4). In melanocytes, the coiled coil structure of myosin Va is important in regulating the trafficking of melanosomes in conjunction with melanophilin and Rab27a (5). Myosin Va regulates trafficking and exocytosis of secretory granules in neuroendocrine cells (reviewed in 6) as well as RNA transport and distribution (7).

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: DARPP-32 (dopamine and cyclic AMP-regulated phosphoprotein, relative molecular mass 32,000) is a cytosolic protein highly enriched in medium-sized spiny neurons of the neostriatum (1). It is a bifunctional signaling molecule that controls serine/threonine kinase and serine/threonine phosphatase activity (2). Dopamine stimulates phosphorylation of DARPP-32 through D1 receptors and activation of PKA. PKA phosphorylation of DARPP-32 at Thr34 converts it into an inhibitor of protein phosphatase 1 (1). DARPP-32 is converted into an inhibitor of PKA when phosphorylated at Thr75 by cyclin-dependent kinase 5 (CDK5) (2). Mice containing a targeted deletion of the DARPP-32 gene exhibit an altered biochemical, electrophysiological, and behavioral phenotype (3).

$305
400 µl
This Cell Signaling Technology antibody is immobilized via covalent binding of primary amino groups to N-hydroxysuccinimide (NHS)-activated Sepharose® beads. Myc-Tag (9B111) Mouse mAb (Sepharose® Bead Conjugate) is useful for the immunoprecipitation of Myc-tagged recombinant proteins.
APPLICATIONS
REACTIVITY
All Species Expected

Application Methods: Immunoprecipitation

Background: Epitope tags are useful for the labeling and detection of proteins using immunoblotting, immunoprecipitation, and immunostaining techniques. Because of their small size, they are unlikely to affect the tagged protein’s biochemical properties.

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Western Blotting

Background: Macrophage-colony stimulating factor (M-CSF, CSF-1) receptor is an integral membrane tyrosine kinase encoded by the c-fms proto-oncogene. M-CSF receptor is expressed in monocytes (macrophages and their progenitors) and drives growth and development of this blood cell lineage. (1-3). Binding of M-CSF to its receptor induces receptor dimerization, activation, and autophosphorylation of cytoplasmic tyrosine residues used as docking sites for SH2-containing signaling proteins (4). There are at least five major tyrosine autophosphorylation sites. Tyr723 (Tyr721 in mouse) is located in the kinase insert (KI) region. Phosphorylated Tyr723 binds the p85 subunit of PI3 kinase as well as PLCγ2 (5). Phosphorylation of Tyr809 provides a docking site for Shc (5). Overactivation of this receptor can lead to a malignant phenotype in various cell systems (6). The activated M-CSF receptor has been shown to be a predictor of poor outcome in advanced epithelial ovarian carcinoma (7) and breast cancer (8).

$134
20 µl
$336
100 µl
APPLICATIONS
REACTIVITY
D. melanogaster, Human, Monkey, Mouse, Rat

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

Background: Phosphorylation of the eukaryotic initiation factor 2 (eIF2) α subunit is a well-documented mechanism to downregulate protein synthesis under a variety of stress conditions. eIF2 binds GTP and Met-tRNAi and transfers Met-tRNA to the 40S subunit to form the 43S preinitiation complex (1,2). eIF2 promotes a new round of translation initiation by exchanging GDP for GTP, a reaction catalyzed by eIF2B (1,2). Kinases that are activated by viral infection (PKR), endoplasmic reticulum stress (PERK/PEK), amino acid deprivation (GCN2), or heme deficiency (HRI) can phosphorylate the α subunit of eIF2 (3,4). This phosphorylation stabilizes the eIF2-GDP-eIF2B complex and inhibits the turnover of eIF2B. Induction of PKR by IFN-γ and TNF-α induces potent phosphorylation of eIF2α at Ser51 (5,6).

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

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

Background: SHP-2 (PTPN11) is a ubiquitously expressed, nonreceptor protein tyrosine phosphatase (PTP). It participates in signaling events downstream of receptors for growth factors, cytokines, hormones, antigens, and extracellular matrices in the control of cell growth, differentiation, migration, and death (1). Activation of SHP-2 and its association with Gab1 is critical for sustained Erk activation downstream of several growth factor receptors and cytokines (2). In addition to its role in Gab1-mediated Erk activation, SHP-2 attenuates EGF-dependent PI3 kinase activation by dephosphorylating Gab1 at p85 binding sites (3). SHP-2 becomes phosphorylated at Tyr542 and Tyr580 in its carboxy-terminus in response to growth factor receptor activation (4). These phosphorylation events are thought to relieve basal inhibition and stimulate SHP-2 tyrosine phosphatase activity (5). Mutations in the corresponding gene result in a pair of clinically similar disorders (Noonan syndrome and LEOPARD syndrome) that may result from abnormal MAPK regulation (6).

$111
20 µl
$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: ZEB family proteins are zinc finger and homeobox domain containing transcription factors. There are two members in mammals, ZEB1 (δ-EF1, TCF8, AREB6) and ZEB2 (SIP1, (ZEB1 and ZEB2 contain two separate Zinc-finger domain and a homeodomain (1). While ZEB proteins mainly function as transcriptional suppressors, they are able to activate transcription, dependent on DNA-context and cell type (1). One of the targets suppressed by ZEB proteins is E-cadherin. Downregulation of E-cadherin is one of the hallmarks of epithelial mesenchymal transition (EMT), a critical feature of normal embryonic development, which is also utilized by malignant epithelial tumors to spread beyond their origin (2-4). ZEB1 mutations are associated with posterior corneal dystrophy, and ZEB2 mutations were reported to be associated with Hirschsprung (HSCR) disease (5-8).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: LRP5 and LRP6 are single-pass transmembrane proteins belonging to the low-density lipoprotein receptor (LDLR)-related protein family. Unlike other members of the LDLR family, LRP5 and LRP6 have four EGF and three LDLR repeats in the extracellular domain, and proline-rich motifs in the cytoplasmic domain (1). They function as co-receptors for Wnt and are required for the canonical Wnt/β-catenin signaling pathway (2,3). LRP5 and LRP6 are highly homologous and have redundant roles during development (4,5). The activity of LRP5 and LRP6 can be inhibited by the binding of some members of the Dickkopf (DKK) family of proteins (6,7). Upon stimulation with Wnt, LRP6 is phosphorylated at multiple sites including Thr1479, Ser1490, and Thr1493 by kinases such as GSK-3 and CK1 (8-10). Phosphorylated LRP6 recruits axin to the membrane and presumably activates β-catenin signaling (8-10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunofluorescence (Immunocytochemistry), Western Blotting

Background: Na+/H+ exchanger regulatory factor (NHERF1 or EBP-50) is one of several related PDZ domain-containing proteins (1). NHERF1 was first identified as a necessary cofactor for cyclic AMP-associated inhibition of Na+/ H+ exchanger isoform 3 (NHE3) (2). NHERF1 is a multifunctional adaptor protein that interacts with receptors and ion transporters via its PDZ domains, and with the ERM family of proteins, including merlin, via its carboxy-terminus (2,3). NHERF1 may play an important role in breast cancer. Estrogen has been found to induce NHERF1 in estrogen receptor-positive breast cancer cells (2,3). Furthermore, NHERF1 has been shown to bind to PDGFR, which is activated in breast carcinomas. NHERF1 has been found to promote the formation of a ternary complex containing PTEN, NHERF1, and PDGFR. Therefore, NHERF1 may function to recruit PTEN to PDGFR to inhibit the activation of PI3K/Akt signaling in normal cells; this mechanism may be disrupted in cancer (4). NHERF1 also binds to the cystic fibrosis transmembrane conductance regulator (CFTR), which functions as an ion channel and has disease-causing mutations in cystic fibrosis (5). Other proposed functions of NHERF1 include testicular differentiation, endosomal recycling, membrane targeting, protein sorting, and trafficking (6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

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

Background: The methylation state of lysine residues in histone proteins is a major determinant of the 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 jumonji domain-containing protein 2 (JMJD2) family, also known as the JmjC domain-containing histone demethylation protein 3 (JHDM3) family, contains four members: JMJD2A/JHDM3A, JMJD2B/JHDM3B, JMJD2C/JHDM3C, and JMJD2D/JHDM3D. In addition to the JmjC domain, these proteins also contain JmjN, PHD, and tudor domains, the latter of which has been shown to bind to methylated histone H3 at Lys4 and Lys9, and methylated histone H4 at Lys20 (4,5). JMJD2 proteins have been shown to demethylate di- and tri-methyl histone H3 at Lys9 and Lys36 and function as both activators and repressors of transcription (6-11). JMJD2A, JMJD2C, and JMJD2D function as coactivators of the androgen receptor in prostate tumor cells (7). In contrast, JMJD2A also associates with Rb and NCoR corepressor complexes and is necessary for transcriptional repression of target genes (8,9). JMJD2B antagonizes histone H3 Lys9 tri-methylation at pericentric heterochromatin (10). JMJD2C, also known as GASC1, is amplified in squamous cell carcinomas and metastatic lung carcinoma and inhibition of JMJD2C expression decreases cell proliferation (11,12). JMJD2C has also been identified as a downstream target of Oct-4 and is critical for the regulation of self-renewal in embryonic stem cells (13).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: c-Kit is a member of the subfamily of receptor tyrosine kinases that includes PDGF, CSF-1, and FLT3/flk-2 receptors (1,2). It plays a critical role in activation and growth in a number of cell types including hematopoietic stem cells, mast cells, melanocytes, and germ cells (3). Upon binding with its stem cell factor (SCF) ligand, c-Kit undergoes dimerization/oligomerization and autophosphorylation. Activation of c-Kit results in the recruitment and tyrosine phosphorylation of downstream SH2-containing signaling components including PLCγ, the p85 subunit of PI3 kinase, SHP2, and CrkL (4). Molecular lesions that impair the kinase activity of c-Kit are associated with a variety of developmental disorders (5), and mutations that constitutively activate c-Kit can lead to pathogenesis of mastocytosis and gastrointestinal stromal tumors (6). Tyr719 is located in the kinase insert region of the catalytic domain. c-Kit phosphorylated at Tyr719 binds to the p85 subunit of PI3 kinase in vitro and in vivo (7).

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

Application Methods: Western Blotting

Background: c-Kit is a member of the subfamily of receptor tyrosine kinases that includes PDGF, CSF-1, and FLT3/flk-2 receptors (1,2). It plays a critical role in activation and growth in a number of cell types including hematopoietic stem cells, mast cells, melanocytes, and germ cells (3). Upon binding with its stem cell factor (SCF) ligand, c-Kit undergoes dimerization/oligomerization and autophosphorylation. Activation of c-Kit results in the recruitment and tyrosine phosphorylation of downstream SH2-containing signaling components including PLCγ, the p85 subunit of PI3 kinase, SHP2, and CrkL (4). Molecular lesions that impair the kinase activity of c-Kit are associated with a variety of developmental disorders (5), and mutations that constitutively activate c-Kit can lead to pathogenesis of mastocytosis and gastrointestinal stromal tumors (6). Tyr719 is located in the kinase insert region of the catalytic domain. c-Kit phosphorylated at Tyr719 binds to the p85 subunit of PI3 kinase in vitro and in vivo (7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Western Blotting

Background: The cytoskeleton consists of three types of cytosolic fibers: microfilaments (actin filaments), intermediate filaments, and microtubules. Major types of intermediate filaments are distinguished by their cell-specific expression: cytokeratins (epithelial cells), glial fibrillary acidic protein (GFAP) (glial cells), desmin (skeletal, visceral, and certain vascular smooth muscle cells), vimentin (mesenchyme origin), and neurofilaments (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). Research studies have shown that vimentin is present in sarcomas, but not carcinomas, and its expression is examined in conjunction with that of other markers to distinguish between the two (3). Vimentin's dynamic structural changes and spatial re-organization in response to extracellular stimuli help to coordinate various signaling pathways (4). Phosphorylation of vimentin at Ser56 in smooth muscle cells regulates the structural arrangement of vimentin filaments in response to serotonin (5,6). Remodeling of vimentin and other intermediate filaments is important during lymphocyte adhesion and migration through the endothelium (7).During mitosis, CDK1 phosphorylates vimentin at Ser56. This phosphorylation provides a PLK binding site for vimentin-PLK interaction. PLK further phosphorylates vimentin at Ser82, which might serve as memory phosphorylation site and play a regulatory role in vimentin filament disassembly (8,9). Additionally, studies using various soft-tissue sarcoma cells have shown that phosphorylation of vimentin at Ser39 by Akt1 enhances cell migration and survival, suggesting that vimentin could be a potential target for soft-tissue sarcoma targeted therapy (10,11).

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

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

Background: LIM-containing lipoma-preferred partner (LPP) belongs to the zyxin family, members of which include LIMD1, ajuba, trip6 and zyxin. Three LIM domains at the carboxy-terminus characterize this family of proteins. Zyxin family members associate with the actin cytoskeleton and are components of both the cell-cell junction adhesive complex and the integrin-mediated adhesive complex (1). They shuttle in and out of the nucleus where they may function in transcriptional activation (1).LPP binding partners at cell-cell contacts include the actin regulator α-actinin (2) and the human tumor suppressor scrib which regulates cell migration and polarity (3).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse

Application Methods: Western Blotting

Background: Ribonucleotide reductase catalyzes the rate-limiting step in the synthesis of deoxynucleotide triphosphates (dNTPs). The regulatory M1 subunit (RRM1) is present throughout the cell division cycle, but downregulated in quiescent cells (1). Research studies have demonstrated that RRM1 is involved in carcinogenesis and tumor progression, and its expression is correlated with resistance to chemotherapy in non-small cell lung cancer (2-4).

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

Application Methods: Western Blotting

Background: The initiation of DNA replication in mammalian cells is a highly coordinated process that ensures duplication of the genome only once per cell division cycle. Origins of replication are dispersed throughout the genome, and their activities are regulated via the sequential binding of pre-replication and replication factors. The origin recognition complex (ORC) is thought to be bound to chromatin throughout the cell cycle (1,2). The pre-replication complex (Pre-RC) forms in late mitosis/early G1 phase beginning with the binding of CDT1 and cdc6 to the origin, which allows binding of the heterohexameric MCM2-7 complex. The MCM complex is thought to be the replicative helicase, and formation of the pre-RC is referred to as chromatin licensing. Subsequent initiation of DNA replication requires the activation of the S-phase promoting kinases cdk2 and cdc7. Cdc7, which is active only in complex with its regulatory subunit dbf4, phosphorylates MCM proteins bound to chromatin and allows binding of the replication factor cdc45 and DNA polymerase (3,4).Replication licensing is controlled in part by the degradation of cdc6 in quiescent cells. Phosphorylation of cdc6 by cdk2 prevents its degradation, allowing pre-replication complexes to form (5). Cdc6 has recently been shown to play an important role in the intra-S-phase p21 Waf1/Cip1-dependent DNA damage response (6,7). Both cdc6 and CDT1 are degraded by the ubiquitin proteasome pathway in response to DNA damage associated with re-replication (8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: The initiation of DNA replication in mammalian cells is a highly coordinated process that ensures duplication of the genome only once per cell division cycle. Origins of replication are dispersed throughout the genome, and their activities are regulated via the sequential binding of prereplication and replication factors. The origin recognition complex (ORC) is thought to be bound to chromatin throughout the cell cycle (1,2). The prereplication complex (Pre-RC) forms in late mitosis/early G1 phase beginning with the binding of CDT1 and cdc6 to the origin, which allows binding of the heterohexameric MCM2-7 complex. The MCM complex is thought to be the replicative helicase, and formation of the pre-RC is referred to as chromatin licensing. Subsequent initiation of DNA replication requires the activation of the S-phase promoting kinases CDK2 and cdc7. Cdc7, which is active only in complex with its regulatory subunit dbf4, phosphorylates MCM proteins bound to chromatin and allows binding of the replication factor cdc45 and DNA polymerase (3,4).Binding of CDT1 to geminin prevents pre-RC formation, and expression and degradation of geminin serve to regulate CDT1 activity (reviewed in 5). The interaction of CDT1 with MCM proteins is important in pre-RC formation and licensing (6,7). Both cdc6 and CDT1 are degraded by the ubiquitin proteasome pathway in response to DNA damage associated with rereplication (8).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: N-methyl-D-aspartate receptor (NMDAR) forms a heterodimer of at least one NR1 and one NR2A-D subunit. Multiple receptor isoforms with distinct brain distributions and functional properties arise by selective splicing of the NR1 transcripts and differential expression of the NR2 subunits. NR1 subunits bind the co-agonist glycine and NR2 subunits bind the neurotransmitter glutamate. Activation of the NMDA receptor or opening of the ion channel allows flow of Na+ and Ca2+ ions into the cell, and K+ out of the cell (1). Each subunit has a cytoplasmic domain that can be directly modified by the protein kinase/phosphatase (2). PKC can phosphorylate the NR1 subunit (NMDAR1) of the receptor at Ser890/Ser896, and PKA can phosphorylate NR1 at Ser897 (3). The phosphorylation of NR1 by PKC decreases its affinity for calmodulin, thus preventing the inhibitory effect of calmodulin on NMDAR (4). The phosphorylation of NR1 by PKA probably counteracts the inhibitory effect of calcineurin on the receptor (5). NMDAR mediates long-term potentiation and slow postsynaptic excitation, which play central roles in learning, neurodevelopment, and neuroplasticity (6).

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: N-methyl-D-aspartate receptor (NMDAR) forms a heterodimer of at least one NR1 and one NR2A-D subunit. Multiple receptor isoforms with distinct brain distributions and functional properties arise by selective splicing of the NR1 transcripts and differential expression of the NR2 subunits. NR1 subunits bind the co-agonist glycine and NR2 subunits bind the neurotransmitter glutamate. Activation of the NMDA receptor or opening of the ion channel allows flow of Na+ and Ca2+ ions into the cell, and K+ out of the cell (1). Each subunit has a cytoplasmic domain that can be directly modified by the protein kinase/phosphatase (2). PKC can phosphorylate the NR1 subunit (NMDAR1) of the receptor at Ser890/Ser896, and PKA can phosphorylate NR1 at Ser897 (3). The phosphorylation of NR1 by PKC decreases its affinity for calmodulin, thus preventing the inhibitory effect of calmodulin on NMDAR (4). The phosphorylation of NR1 by PKA probably counteracts the inhibitory effect of calcineurin on the receptor (5). NMDAR mediates long-term potentiation and slow postsynaptic excitation, which play central roles in learning, neurodevelopment, and neuroplasticity (6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Western Blotting

Background: Cathepsin B (CSTB), part of the papain family of proteases, is a widely expressed lysosomal cysteine endopeptidase (1,2). Cathepsin B is produced from a larger precursor form, pro-cathepsin B, which runs at approximately 44 kDa on SDS-PAGE, and is proteolytically processed and glycosylated to form a mature two-chain protein containing a heavy chain (running at 27 and 24 kDa) and a light chain (5 kDa). High levels of cathepsin B are found in macrophages and osteoclasts, as well as various types of cancer cells, including lung, colon, prostate, breast, and stomach. In addition, expression of cathepsin B has been associated with multiple sclerosis (3), rheumatoid arthritis (4), and pancreatitis (5). While generally localized to lysosomes, in cancer alterations can lead to its secretion (6). Its role in tumor progression is thought to involve promotion of basement membrane degradation, invasion and metastasis (7,8). Expression can correlate with poor prognosis for a variety of forms of cancer (9-13).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Na+/H+ exchanger regulatory factor (NHERF1 or EBP-50) is one of several related PDZ domain-containing proteins (1). NHERF1 was first identified as a necessary cofactor for cyclic AMP-associated inhibition of Na+/ H+ exchanger isoform 3 (NHE3) (2). NHERF1 is a multifunctional adaptor protein that interacts with receptors and ion transporters via its PDZ domains, and with the ERM family of proteins, including merlin, via its carboxy-terminus (2,3). NHERF1 may play an important role in breast cancer. Estrogen has been found to induce NHERF1 in estrogen receptor-positive breast cancer cells (2,3). Furthermore, NHERF1 has been shown to bind to PDGFR, which is activated in breast carcinomas. NHERF1 has been found to promote the formation of a ternary complex containing PTEN, NHERF1, and PDGFR. Therefore, NHERF1 may function to recruit PTEN to PDGFR to inhibit the activation of PI3K/Akt signaling in normal cells; this mechanism may be disrupted in cancer (4). NHERF1 also binds to the cystic fibrosis transmembrane conductance regulator (CFTR), which functions as an ion channel and has disease-causing mutations in cystic fibrosis (5). Other proposed functions of NHERF1 include testicular differentiation, endosomal recycling, membrane targeting, protein sorting, and trafficking (6).

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunofluorescence (Frozen), Western Blotting

Background: N-methyl-D-aspartate receptor (NMDAR) forms a heterodimer of at least one NR1 and one NR2A-D subunit. Multiple receptor isoforms with distinct brain distributions and functional properties arise by selective splicing of the NR1 transcripts and differential expression of the NR2 subunits. NR1 subunits bind the co-agonist glycine and NR2 subunits bind the neurotransmitter glutamate. Activation of the NMDA receptor or opening of the ion channel allows flow of Na+ and Ca2+ ions into the cell, and K+ out of the cell (1). Each subunit has a cytoplasmic domain that can be directly modified by the protein kinase/phosphatase (2). PKC can phosphorylate the NR1 subunit (NMDAR1) of the receptor at Ser890/Ser896, and PKA can phosphorylate NR1 at Ser897 (3). The phosphorylation of NR1 by PKC decreases its affinity for calmodulin, thus preventing the inhibitory effect of calmodulin on NMDAR (4). The phosphorylation of NR1 by PKA probably counteracts the inhibitory effect of calcineurin on the receptor (5). NMDAR mediates long-term potentiation and slow postsynaptic excitation, which play central roles in learning, neurodevelopment, and neuroplasticity (6).

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

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

Background: Protein arginine N-methyltransferase 1 (PRMT1) is a member of the protein arginine N-methyltransferase (PRMT) family of proteins that catalyze the transfer of a methyl group from S-adenosylmethionine (AdoMet) to a guanidine nitrogen of arginine (1). Though all PRMT proteins catalyze the formation of mono-methyl arginine, Type I PRMTs (PRMT1, 3, 4, and 6) add an additional methyl group to produce an asymmetric di-methyl arginine while Type II PRMTs (PRMT 5 and 7) produce symmetric di-methyl arginine (1). Mono-methyl arginine, but not di-methyl arginine, can be converted to citrulline through deimination catalyzed by enzymes such as PADI4 (2). Most PRMTs, including PRMT1, methylate arginine residues found within glycine-arginine rich (GAR) protein domains, such as RGG, RG, and RXR repeats (1). However, PRMT4/CARM1 and PRMT5 methylate arginine residues within PGM (proline-, glycine-, methionine-rich) motifs (3). PRMT1 methylates Arg3 of histone H4 and cooperates synergistically with p300/CBP to enhance transcriptional activation by nuclear receptor proteins (4-6). In addition, PRMT1 methylates many non-histone proteins, including the orphan nuclear receptor HNF4 (6), components of the heterogeneous nuclear ribonucleoprotein (hnRNP) particle (7), the RNA binding protein Sam68 (8), interleukin enhancer-binding factor 3 (ILF3) (9) and interferon-α and β receptors (10). These interactions suggest additional functions in transcriptional regulation, mRNA processing and signal transduction. Alternative mRNA splicing produces three enzymatically active PRMT1 isoforms that differ in their amino-terminal regions (11). PRMT1 is localized to the nucleus or cytoplasm, depending on cell type (12,13), and appears in many distinct protein complexes. ILF3, TIS21 and the leukemia-associated BTG1 proteins bind PRMT1 to regulate its methyltransferase activity (9,14).