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Product listing: Phospho-Gab1 (Tyr659) Antibody, UniProt ID Q13480 #12745 to CaSR (D6D9V) Rabbit mAb, UniProt ID P41180 #73303

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: The Grb-associated binder (Gab) family is a family of adaptor proteins recruited by a wide variety of receptor tyrosine kinases (RTKs) such as EGFR, HGFR, insulin receptor, cytokine receptor and B cell antigen receptors. Upon stimulation of RTKs by their cognate ligand, Gab is recruited to the plasma membrane where it is phosphorylated and functions as a scaffold (1-4). Multiple tyrosine phosphorylation sites of Gab1 protein have been identified (5). Phosphorylation of Tyr472 regulates its binding to p85 PI3 kinase (6,7). Phosphorylation of Gab1 at Tyr307, Tyr373 and Tyr407 modulates its association to PLCγ (8). Phosphorylation of Tyr627 and Tyr659 is required for Gab1 binding to and activation of the protein tyrosine phosphatase SHP2 (6,9).

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Immunoprecipitation, Western Blotting

Background: Bim/Bod is a pro-apoptotic protein belonging to the BH3-only group of Bcl-2 family members including Bad, Bid, Bik, Hrk, and Noxa that contain a BH3 domain but lack other conserved BH1 or BH2 domains (1,2). Bim induces apoptosis by binding to and antagonizing anti-apoptotic members of the Bcl-2 family. Interactions have been observed with Bcl-2, Bcl-xL, Mcl-1, Bcl-w, Bfl-1, and BHRF-1 (1,2). Bim functions in regulating apoptosis associated with thymocyte negative selection and following growth factor withdrawal, during which Bim expression is elevated (3-6). Three major isoforms of Bim are generated by alternative splicing: BimEL, BimL, and BimS (1). The shortest form, BimS, is the most cytotoxic and is generally only transiently expressed during apoptosis. The BimEL and BimL isoforms may be sequestered to the dynein motor complex through an interaction with the dynein light chain and released from this complex during apoptosis (7). Apoptotic activity of these longer isoforms may be regulated by phosphorylation (8,9). Environmental stress triggers Bim phosphorylation by JNK and results in its dissociation from the dynein complex and increased apoptotic activity.

$293
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Chromatin IP, Immunoprecipitation, Western Blotting

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

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Fibroblast growth factors (FGFs) produce mitogenic and angiogenic effects in target cells by signaling through cell surface receptor tyrosine kinases. There are four members of the FGF receptor family: FGFR1 (flg), FGFR2 (bek, KGFR), FGFR3, and FGFR4. Each receptor contains an extracellular ligand binding domain, a transmembrane domain, and a cytoplasmic kinase domain (1). Following ligand binding and dimerization, the receptors are phosphorylated at specific tyrosine residues (2). Seven tyrosine residues in the cytoplasmic tail of FGFR1 can be phosphorylated: Tyr463, 583, 585, 653, 654, 730, and 766. Tyr653 and Tyr654 are important for catalytic activity of activated FGFR and are essential for signaling (3). The other phosphorylated tyrosine residues may provide docking sites for downstream signaling components such as Crk and PLCγ (4,5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunofluorescence (Immunocytochemistry), 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).

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Activation of protein kinase C (PKC) is one of the earliest events in a cascade that controls a variety of cellular responses, including secretion, gene expression, proliferation, and muscle contraction (1,2). PKC isoforms belong to three groups based on calcium dependency and activators. Classical PKCs are calcium-dependent via their C2 domains and are activated by phosphatidylserine (PS), diacylglycerol (DAG), and phorbol esters (TPA, PMA) through their cysteine-rich C1 domains. Both novel and atypical PKCs are calcium-independent, but only novel PKCs are activated by PS, DAG, and phorbol esters (3-5). Members of these three PKC groups contain a pseudo-substrate or autoinhibitory domain that binds to substrate-binding sites in the catalytic domain to prevent activation in the absence of cofactors or activators. Control of PKC activity is regulated through three distinct phosphorylation events. Phosphorylation occurs in vivo at Thr500 in the activation loop, at Thr641 through autophosphorylation, and at the carboxy-terminal hydrophobic site Ser660 (2). Atypical PKC isoforms lack hydrophobic region phosphorylation, which correlates with the presence of glutamic acid rather than the serine or threonine residues found in more typical PKC isoforms. The enzyme PDK1 or a close relative is responsible for PKC activation. A recent addition to the PKC superfamily is PKCμ (PKD), which is regulated by DAG and TPA through its C1 domain. PKD is distinguished by the presence of a PH domain and by its unique substrate recognition and Golgi localization (6). PKC-related kinases (PRK) lack the C1 domain and do not respond to DAG or phorbol esters. Phosphatidylinositol lipids activate PRKs, and small Rho-family GTPases bind to the homology region 1 (HR1) to regulate PRK kinase activity (7).

$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. The antibody is expected to exhibit the same species cross-reactivity as the unconjugated α-Tubulin (11H10) Rabbit mAb #2125.
APPLICATIONS
REACTIVITY
Bovine, D. melanogaster, Human, Monkey, Mouse, Pig, Rat, Zebrafish

Application Methods: Flow Cytometry, Immunofluorescence (Immunocytochemistry)

Background: The cytoskeleton consists of three types of cytosolic fibers: microtubules, microfilaments (actin filaments), and intermediate filaments. Globular tubulin subunits comprise the microtubule building block, with α/β-tubulin heterodimers forming the tubulin subunit common to all eukaryotic cells. γ-tubulin is required to nucleate polymerization of tubulin subunits to form microtubule polymers. Many cell movements are mediated by microtubule action, including the beating of cilia and flagella, cytoplasmic transport of membrane vesicles, chromosome alignment during meiosis/mitosis, and nerve-cell axon migration. These movements result from competitive microtubule polymerization and depolymerization or through the actions of microtubule motor proteins (1).

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

Application Methods: Western Blotting

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

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Neural precursor expressed, developmentally down-regulated protein 4 (NEDD4) was originally identified as a gene that is highly expressed in the early mouse embryonic central nervous system (1). Subsequently, a family of NEDD4-like proteins have been defined that includes seven members in humans (2). NEDD4 and NEDD4-like (NEDD4L) proteins contain multiple functional domains including a calcium-dependent phospholipid and membrane binding domain (C2 domain), two to four protein binding domains (WW domains), and an E3 ubiquitin-protein ligase domain (HECT domain). NEDD4 and NEDD4L have been shown to downregulate both neuronal voltage-gated Na+ channels (NaVs) and epithelial Na+ channels (ENaCs) in response to increased intracellular Na+ concentrations (3,4). The WW domains of NEDD4 bind to PY motifs (amino acid sequence PPXY) found in multiple NaV and ENaC proteins; ubiquitination of these proteins is mediated by the HECT domain of NEDD4 and results in their internalization and removal from the plasma membrane. Research studies have shown that mutation of the PY motifs in ENaC proteins is associated with Liddle's syndrome, an autosomal dominant form of hypertension (5). In addition to targeting sodium channels, NEDD4L has also been shown to negatively regulate TGF-β signaling by targeting Smad2 for degradation (6). Mouse and human NEDD4 are rapidly cleaved by caspase proteins during apoptosis, although the significance of this cleavage is not clear (7).

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Immunoprecipitation, Western Blotting

Background: Embryonic stem cells (ESC) derived from the inner cell mass of the blastocyst are unique in their pluripotent capacity and potential for self-renewal (1). Research studies demonstrate that a set of transcription factors that includes Oct-4, Sox2, and Nanog forms a transcriptional network that maintains cells in a pluripotent state (2,3). Chromatin immunoprecipitation experiments show that Sox2 and Oct-4 bind to thousands of gene regulatory sites, many of which regulate cell pluripotency and early embryonic development (4,5). siRNA knockdown of either Sox2 or Oct-4 results in loss of pluripotency (6). Induced overexpression of Oct-4 and Sox2, along with additional transcription factors Klf4 and c-Myc, can reprogram both mouse and human somatic cells to a pluripotent state (7,8). Additional evidence demonstrates that Sox2 is also present in adult multipotent progenitors that give rise to some adult epithelial tissues, including several glands, the glandular stomach, testes, and cervix. Sox2 is thought to regulate target gene expression important for survival and regeneration of these tissues (9).

$303
100 µl
APPLICATIONS
REACTIVITY
Rat

Application Methods: 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
All Species Expected, Human

Application Methods: Western Blotting

Background: The MAPK and CDK families of serine/threonine protein kinases play important roles in proliferation and cell cycle control. These kinases phosphorylate threonine or serine followed by a proline residue (1-3). MAPK phosphorylates substrates with the consensus sequence PX(S/T)P, and CDKs phosphorylate substrates containing the consensus sequence (S/T)PXR/K. Cell Signaling Technology has developed antibodies that bind to phospho-threonine followed by proline, motifs PXS*/T*P and/or S*PXR/K, for use in the study and discovery of new MAPK and CDK substrates (4,5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: CDGSH iron-sulfur domain-containing protein 1 (CISD1), also known as mitochondrial outer membrane iron-sulfur (2Fe-2S) protein (mitoNEET) was first identified as the target for the drug pioglitazone, used to treat diabetes (1-3). CISD1/mitoNEET regulates both mitochondrial iron transport into the matrix and mitochondrial respiratory capacity. It has also been shown to affect the dynamics of cellular and whole-body lipid homeostasis (2,4). Furthermore, research studies have shown that CISD1/mitoNEET is overexpressed in human epithelial breast cancer cells and it has been considered a potential chemotherapeutic target (6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Immunoprecipitation, Western Blotting

Background: DNA double-strand breaks (DSBs) are potentially hazardous lesions that can be induced by ionizing radiation (IR), radiomimetic chemicals, or DNA replication inhibitors. Cells recognize and repair DSBs via two distinct but partly overlapping signaling pathways, nonhomologous end joining (NHEJ) and homologous recombination (HR). DNA repair via the HR pathway is restricted to S and G2 phases of the cell cycle, while NHEJ can occur during any phase. Defects in both pathways have been associated with human disease, including cancer (1).Artemis is a ubiquitously expressed NHEJ factor that exhibits endonuclease activity. Artemis functions in DNA repair by promoting nonhomologous end joining (2), as well as in cell cycle checkpoint control through ATM/ATR signaling (3).NHEJ machinery is also utilized in V(D)J recombination, a process that generates diversity in immunoglobulin and T cell receptor genes, and artemis is a key factor in this process (4,5). Mutations in the corresponding artemis gene (DCLRE1C) are associated with a radiosensitive type of severe combined immunodeficiency (SCID) in humans (6,7).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: The Ret proto-oncogene (c-Ret) is a receptor tyrosine kinase that functions as a multicomponent receptor complex in conjunction with other membrane-bound, ligand-binding GDNF family receptors (1). Ligands that bind the Ret receptor include the glial cell line-derived neurotrophic factor (GDNF) and its congeners neurturin, persephin, and artemin (2-4). Research studies have shown that alterations in the corresponding RET gene are associated with diseases including papillary thyroid carcinoma, multiple endocrine neoplasia (type 2A and 2B), familial medullary thyroid carcinoma, and a congenital developmental disorder known as Hirschsprung’s disease (1,3). The Tyr905 residue located in the Ret kinase domain plays a crucial role in Ret catalytic and biological activity. Substitution of Phe for Tyr at position 905 dramatically inhibits Ret autophosphorylation activity (5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: The nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) family of proteins is a diverse family of cytoplasmic innate immune receptors. They are characterized by the presence of an amino-terminal effector domain, which is often either a caspase activation and recruitment domain (CARD) or a pyrin domain (PYD), followed by a NACHT domain and carboxy-terminal leucine-rich-repeats (LRR) involved in recognition of pathogen-associated molecular patterns (PAMPs) (1). NLR proteins play a variety of roles during the innate immune response including pathogen sensing, transcriptional activation of proinflammatory cytokines through NF-κB, transcriptional activation of type I interferons through IRFs, and formation of inflammasomes leading to activation of inflammatory caspases (1-7).

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

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

Background: Heterogeneous nuclear ribonucleoprotein K (hnRNP K) belongs to a family of RNA binding multiprotein complexes (hnRNP proteins) that facilitate pre-mRNA processing and transport of mRNA from the nucleus to cytoplasm (1-3). hnRNP K contains three unique structural motifs termed KH domains that bind poly(C) DNA and RNA sequences (4,5). Intricate architecture enables hnRNP K to facilitate mRNA biosynthesis (6), transcriptional regulation (7), and signal transduction. Research studies have shown that cytoplasmic hnRNP K expression is increased in oral squamous cell carcinoma and pancreatic cancer, and may be a potential prognostic factor (8,9). hnRNP K coordinates with p53 to regulate its target gene transcription in response to DNA damage. Proteasome degradation of hnRNP K is mediated by E3 ligase MDM2 (10). The interaction between hnRNP K and c-Src leads to hnRNP K phosphorylation, which allows for hnRNP K activation of silenced mRNA translation (11).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Microtubule associated proteins regulate the stability of microtubules and control processes such as cell polarity/differentiation, neurite outgrowth, cell division and organelle trafficking (1). The MARK (MAP/microtubule affinity-regulating kinases) family (MARK1-4) of serine/threonine kinases was identified based on their ability to phosphorylate microtubule-associated proteins (MAPs) including tau, MAP2 and MAP4 (2-6). MARK proteins phosphorylate MAPs within their microtubule binding domains, causing dissociation of MAPs from microtubules and increased microtubule dynamics (2-4). In the case of tau, phosphorylation has been hypothesized to contribute to the formation of neurofibrillary tangles observed in Alzheimer's disease. Overexpression of MARK leads to hyperphosphorylation of MAPs, morphological changes and cell death (4). The tumor suppressor kinase LKB1 phosphorylates MARK and the closely related AMP-kinases within their T-loops, leading to increased activity (7).

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

Application Methods: Western Blotting

Background: High temperature requirement protein A2 (HtrA2)/Omi is a serine protease with homology to the E. coli HtrA protein (DegP) and is thought to be involved in apoptosis and stress-induced degradation of misfolded proteins (1). While HtrA2 was orignally identified to be present in either the nucleus (1) or endoplasmic reticulum (2), subsequent studies have shown that it localizes in mitochondria and is released during apoptosis (3-8). HtrA2 is produced as a 50 kDa zymogen that is cleaved to generate a 36 kDa mature protein that exposes an amino terminal motif (AVPS) resembling that of the IAP inhibitor Smac/Diablo (3-8). Like Smac, interaction between HtrA2 and IAP family members, such as XIAP, antagonizes their inhibition of caspase activity and protection from apoptosis (3-8). Interestingly, HtrA2 knock-out mice did not show signs of reduced apoptosis, but rather had a loss of neurons in the striatum and a Parkinson's-like phenotype, suggesting that HtrA2 might have a neuroprotective function (9-11). This activity is associated with the protease activity of HtrA2 (9). Furthermore, research studies have shown that loss of function mutations in the HtrA2 gene are associated with Parkinson's disease (12).

$269
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

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

Background: TDP43 (TAR DNA-binding protein 43) is involved in transcriptional regulation and exon splicing (1,2). While normal TDP43 is a nuclear protein, pathological TDP43 is a component of insoluble aggregates in patients with frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). In these disorders, TDP43 is abnormally ubiquitinated, phosphorylated and cleaved to generate carboxy-terminal fragments that are sequestered as insoluble aggregates in neuronal nuclei, perikarya, and neurites (3,4). Additionally, TDP43 inhibits the expression of the HIV-1 gene and regulates CFTR gene splicing (1,5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: TCF12/HEB (T cell factor 12/HeLa E-box binding protein) is a member of the E proteins that are type I basic helix-loop-helix domain containing transcription factors that bind directly to the E-box DNA consensus sequence and control numerous developmental processes (1,2). E protein family members include E2A, E2-2, and TCF12/HEB. TCF12/HEB forms homo- or heterodimers with other E proteins to regulate transcription of target genes that play a critical role in the development of T cells, B cells, and plasmacytoid dendritic cells (2-4). The TCF12/HEB gene has two transcriptional start sites leading to the generation of the long form called HEBCan, and the short form, HEBAlt (5). The two isoforms are thought to have distinct functions with HEBCan playing a role throughout T cell development, while HEBAlt functions in the efficient generation of T cell precursors (5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: TTK (Mps1, PYT) is a cell cycle regulated dual specificity kinase present in rapidly proliferating tissues and cell lines (1-3). TTK localizes to kinetochores and centromeres and is an essential component of the mitotic spindle checkpoint as well as centrosome duplication (4-6). The mitotic checkpoint inhibits entry into anaphase until all chromosomes are attached to the spindle; inhibition of this process leads to genomic instability and tumorigenesis. Phosphorylation of the BLM helicase at Ser144 by TTK maintains chromosome stability during mitosis (7). Small molecule inhibitors of TTK can block the spindle checkpoint response, thereby making TTK a potential therapeutic target (8,9).TTK also participates in the DNA damage response by directly phosphorylating and activating the cell cycle checkpoint kinase Chk2 at Thr68. Two targets phosphorylated by Chk2 are the cell cycle phosphatase cdc25 and the transcription factor p53. Inactivation of cdc25 phosphatase results in the accumulation of inactive cyclin B and cell cycle arrest following DNA damage. Phosphorylation of p53 by active Chk2 stabilizes the transcription factor and promotes cell cycle arrest and apoptosis in response to DNA damage (10).

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

Application Methods: Western Blotting

Background: Rap1 and Rap2 belong to the Ras subfamily of small GTPases and are activated by a wide variety of stimuli through integrins, receptor tyrosine kinases (RTKs), G-protein coupled receptors (GPCR), death domain associated receptors (DD-R) and ion channels (1,2). Like other small GTPases, Rap activity is stimulated by guanine nucleotide exchange factors (GEF) and inactivated by GTPase activating proteins (GAP). A wide variety of Rap GEFs have been identified: C3G connects Rap1 with RTKs through adaptor proteins such as Crk, Epacs (or cAMP-GEFs) transmit signals from cAMP, and CD-GEFs (or CalDAG-GEFs) convey signals from either or both Ca2+ and DAG (1). Rap1 primarily regulates multiple integrin-dependent processes such as morphogenesis, cell-cell adhesion, hematopoiesis, leukocyte migration and tumor invasion (1,2). Rap1 may also regulate proliferation, differentiation and survival through downstream effectors including B-Raf, PI3K, RalGEF and phospholipases (PLCs) (1-4). Rap1 and Rap2 are not fuctionally redundant as they perform overlapping but distinct functions (5). Recent research indicates that Rap2 regulates Dsh subcellular localization and is required for Wnt signaling in early development (6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

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

Background: The DNA mismatch repair system (MMR) repairs post-replication DNA, inhibits recombination between non-identical DNA sequences and induces both checkpoint and apoptotic responses following certain types of DNA damage (1). MSH2 (MutS homologue 2) forms the hMutS-α dimer with MSH6 and is an essential component of the mismatch repair process. hMutS-α is part of the BRCA1-associated surveillance complex (BASC), a complex that also contains BRCA1, MLH1, ATM, BLM, PMS2 proteins and the Rad50-Mre11-NBS1 complex (2).Mutations in MSH2 have been found in a large proportion of hereditary non-polyposis colorectal cancer (Lynch Syndrome), the most common form of inherited colorectal cancer in the Western world (3). Mutations have also been associated with other sporadic tumors.

$269
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse, Rat

Application Methods: Immunohistochemistry (Paraffin), Western Blotting

Background: The modulation of chromatin structure is an essential component in the regulation of transcriptional activation and repression. Modifications can be made by at least two evolutionarily conserved strategies, through the disruption of histone-DNA contacts by ATP-dependent chromatin remodelers, or by histone tail modifications including methylation and acetylation. One of the four classes of ATP-dependent histone remodelers is the SWI/SNF complex, the central catalytic subunit of which is Brg1 or the highly related protein hBRM (1). This SWI/SNF complex contains varying subunits but its association with either Brg1 or hBRM remains constant (1). SWI/SNF complexes have been shown to regulate gene activation, cell growth, the cell cycle and differentiation (1). Brg1/hBRM have been shown to regulate transcription through enhancing transcriptional activation of glucocorticoid receptors (2). Although usually associated with transcriptional activation, Brg1/hBRM have also been found in complexes associated with transcriptional repression including with HDACs, Rb and Tif1β (3-5). Brg1/hBRM plays a vital role in the regulation of gene transcription during early mammalian embryogenesis. In addition, Brg1/hBRM also play a role as a tumor suppressors and Brg1 is mutated in several tumor cell lines (6-8).

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

Application Methods: Western Blotting

Background: Translationally controlled tumor protein (TCTP/p23/HRF) is a ubiquitously expressed and highly conserved protein involved in various cellular processes, such as its role as a histamine releasing factor in chronic allergic disease (1). TCTP binds tubulin in a cell cycle dependent manner and is associated with the mitotic spindle (2). In addition, TCTP interacts with the actin cytoskeleton to regulate cell shape (3). In mitosis, TCTP is phosphorylated by PLK at Ser46, decreasing microtubule stability (4,5). TCTP interacts with the small GTPase Rheb, possibly acting as a GEF, thereby activating the TORC1 pathway and controlling cell growth and proliferation (6,7). TCTP has also been shown to be involved in apoptosis and cell stress (8-11). In cultured cells, reduction in TCTP expression can cause loss of the malignant phenotype (12).

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

Application Methods: Western Blotting

Background: The epidermal growth factor (EGF) receptor is a transmembrane tyrosine kinase that belongs to the HER/ErbB protein family. Ligand binding results in receptor dimerization, autophosphorylation, activation of downstream signaling, internalization, and lysosomal degradation (1,2). Phosphorylation of EGF receptor (EGFR) at Tyr845 in the kinase domain is implicated in stabilizing the activation loop, maintaining the active state enzyme, and providing a binding surface for substrate proteins (3,4). c-Src is involved in phosphorylation of EGFR at Tyr845 (5). The SH2 domain of PLCγ binds at phospho-Tyr992, resulting in activation of PLCγ-mediated downstream signaling (6). Phosphorylation of EGFR at Tyr1045 creates a major docking site for the adaptor protein c-Cbl, leading to receptor ubiquitination and degradation following EGFR activation (7,8). The GRB2 adaptor protein binds activated EGFR at phospho-Tyr1068 (9). A pair of phosphorylated EGFR residues (Tyr1148 and Tyr1173) provide a docking site for the Shc scaffold protein, with both sites involved in MAP kinase signaling activation (2). Phosphorylation of EGFR at specific serine and threonine residues attenuates EGFR kinase activity. EGFR carboxy-terminal residues Ser1046 and Ser1047 are phosphorylated by CaM kinase II; mutation of either of these serines results in upregulated EGFR tyrosine autophosphorylation (10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Mouse

Application Methods: Western Blotting

Background: Insulin-like growth factor-II mRNA-binding proteins (IMPs) belong to a family of zipcode-binding proteins (1,2). Three members of this family, IMP1, IMP2, and IMP3, have been identified (1,2). They contain two RNA recognition motifs, four K homology domains, and were found to function in mRNA localization, turnover, and translation control (1,2). Research studies have implicated these proteins in a variety of physiological and pathological processes, such as growth and development (3), testicular neoplasia (4), and melanocytic neoplasia (5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Thymidine phosphorylase (TP) is a platelet-derived endothelial cell growth factor (PD-ECGF) that catalyzes the formation of thymine and 2-deoxy-D-ribose-1-phosphate from thymidine and orthophosphate (1). This intracellular enzyme is capable of both promoting angiogenesis and inhibiting apoptosis. Thymidine phosphorylase catalytic activity is required for its angiogenic function (2,3). Increased expression of TP/PD-ECGF is seen in a wide variety of different solid tumors and inflammatory diseases and is often associated with poor prognosis (4,5). Alternatively, TP can activate fluorouracil derivative (DFUR) prodrugs and increase the antitumor activity of the related treatment (1,5). The use of thymidine phosphorylase as a cancer therapeutic target has been studied extensively, with emphasis on either inhibiting TP enzymatic activity or increasing enzyme induction with concomitant DFUR treatment (1,5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Immunoprecipitation, Western Blotting

Background: CaSR, the extracellular Calcium-Sensing Receptor, is a widely expressed G-protein coupled receptor (GPCR) involved in calcium homeostasis. CaSR operates as a sensor in parathyroid and kidney, and alterations in its activity have been shown to cause thyroid disease in humans (1). Activation of the receptor in response to extracellular calcium or other ligands causes activation of phospholipase C (PLC), release of IP3 and release of calcium from intracellular stores (2). Proinflammatory cytokines IL-1β and TNF-α increase CaSR gene expression in human thyroid and kidney cells through activation of the NF-κB pathway, and this pathway may be involved in hypocalcemia often seen in critically ill patients (3). Elevated calcium concentration and CaSR expression have been linked to proliferation and metastasis of skeletal metastatic prostate cancer cell lines (4). In intestinal epithelial cells, CaSR is involved in regulation of cyclic nucleotide metabolism and the fluid secretion that results in life-threatening fluid loss in response to intestinal pathogens (5). The interaction of CaSR with the actin-binding protein filamin may provide scaffolding for the organization of signaling pathways converging on the cytoskeleton, including CaSR-mediated MAPK pathway activation (6).