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Polyclonal Antibody Regulation of Catalytic Activity

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Protein phosphatase-1 nuclear targeting subunit (PNUTS) is one of the key regulators of protein phosphatase 1 (PP1) in the nucleus (1). Via interaction with PP1, PNUTS plays an essential role in multiple cellular processes, including chromatin decondensation (2), DNA damage response (3), and cardiomyocyte apoptosis (4). Notably, PNUTS also regulates the activity of two key tumor suppressors, Rb and p53, through inhibition of PP1 mediated dephosphorylation (5-7). Research studies indicate that PNUTS also sequesters PTEN in the nucleus through direct interaction and inhibits its tumor suppressor function (8). PNUTS is ubiquitously expressed and elevated PNUTS expression is observed in various cancers such as esophageal carcinoma, squamous cell carcinoma, and prostate cancer (1,8).

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

Application Methods: Western Blotting

Background: Presenilin Enhancer 2 (PEN2) is a small integral membrane glycoprotein that contains two recognized transmembrane domains. Both the N- and C-terminal domains are oriented into the lumen of the endoplasmic reticulum (1). PEN2, along with Presenilin 1, Presenilin 2, Nicastrin, and APH-1 form the protein complex γ-secretase (2). The proteinase BACE catalyses the initial step in APP processing by cleaving and releasing soluble APPβ (3). The remaining membrane bound APP is then cleaved by the γ-secretase complex, causing the release of amyloid β-peptide, the main constituent of amyloid plaques. These plaques are a hallmark of Alzheimer’s disease pathology (2). In addition to APP, the γ-secretase complex cleaves several other proteins and necessary presenilin-dependent signaling cascades, including the Notch pathway (4). It was found that PEN2 is an important part of the γ-secretase complex, and knocking it down results in reduced amounts of the complex, resulting in a loss of γ-secretase activity (5).

$303
100 µl
APPLICATIONS
REACTIVITY
Guinea Pig, Human, Mouse

Application Methods: Western Blotting

Background: The phagocytic NADPH oxidase is a multiprotein enzyme that catalyzes the reduction of oxygen to superoxide in response to invasion of pathogens into the body. The NADPH oxidase consists of 6 subunits, the membrane-bound p91phox and p22phox heterodimer (also known as cytochrome b558), the cytoplasmic complex of p40phox, p47phox and p67phox, and the small GTPase Rac2. Activation of NADPH oxidase is initiated by phosphorylation of the cytosolic complex, which induces comformational changes of the complex and ultimately leads to the translocation of the cytoplasmic complex to the membrane to form an active enzyme with cytochrome b558 (1). Thr154 and Ser315 of p40 phox have been identified as PKC phosphorylation sites modified during activation of the phagocyte NADPH oxidase (2).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Arrestin proteins function as negative regulators of G protein-coupled receptor (GPCR) signaling. Cognate ligand binding stimulates GPCR phosphorylation, which is followed by binding of arrestin to the phosphorylated GPCR and the eventual internalization of the receptor and desensitization of GPCR signaling (1). Four distinct mammalian arrestin proteins are known. Arrestin 1 (also known as S-arrestin) and arrestin 4 (X-arrestin) are localized to retinal rods and cones, respectively. Arrestin 2 (also known as β-arrestin 1) and arrestin 3 (β-arrestin 2) are ubiquitously expressed and bind to most GPCRs (2). β-arrestins function as adaptor and scaffold proteins and play important roles in other processes, such as recruiting c-Src family proteins to GPCRs in Erk activation pathways (3,4). β-arrestins are also involved in some receptor tyrosine kinase signaling pathways (5-8). Additional evidence suggests that β-arrestins translocate to the nucleus and help regulate transcription by binding transcriptional cofactors (9,10).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Western Blotting

Background: Pitrilysin metalloproteinase 1 (PITRM1 or PreP) is a mitochondria-enriched presequence peptidase that processes the mitochondrial targeting sequence (MTS) of proteins imported across the inner mitochondrial membrane (1). Mitochondria normally function to regulate many cellular processes such as energy production and apoptosis, and its dysfunction may contribute indirectly or directly to human neurodegenerative diseases like Alzheimer’s and Parkinson’s disease (2, 3; AD and PD, respectively). Interestingly, Aβ, the pathological hallmark of AD, accumulates in mitochondria and inhibits Cym1, the PITRM1 yeast ortholog, leading to impaired MTS processing and accumulation of unprocessed mitochondrial proteins, suggesting an indirect role of Aβ and mitochondrial dysfunction via PITRM1 (4). In addition to biochemical association of PITRM1 with Aβ-dependent mitochondrial dysfunction, human genetics suggest a more direct link as PITRM1 genetic variants have been associated with AD (5, 6). The specific mechanism is currently poorly understood, but may involve impairment of PITRM1-dependent degradation of Aβ, directly resulting in pathological accumulation of Aβ in mitochondria (6).

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

Application Methods: Western Blotting

Background: Nicastrin is a transmembrane glycoprotein serving as an essential component of the γ-secretase complex (1,2). Nicastrin is physically associated with presenilin and plays an important role in the stabilization and correct localization of presenilin to the membrane-bound γ-secretase complex (3). Nicastrin also serves as a docking site for γ-secretase substrates such as APP and Notch, directly binding to them and properly presenting them to γ-secretase to ensure the correct cleavage process (2,4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Western Blotting

Background: Glucuronidation is a major pathway that enhances the elimination of lipophilic xenobiotics and endobiotics to more more water soluble compounds for excretion (1,2). The UDP-glucuronosyltransferase (UGT) superfamily catalyzes the glucuronidation of the glycosyl group of a nucleotide sugar to a variety of endogenous and exogenous compounds. Over 100 UGT mammalian gene products have been described and have been divided into subfamilies based on sequence identities (3). The UGT1 subfamily consists of a number of gene products resulting from alternative splicing. These UGT products can differ in tissue expression and substrate specificity. Also, marked differences in the individual expression of UGT isoforms can account for differences in drug metabolism.

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey

Application Methods: Immunoprecipitation, Western Blotting

Background: TFIIF is a member of the group of general transcription factors that facilitate the binding of RNA polymerase II (Pol II) to promoter sequences as part of the pre-initiation complex (PIC) (1). TFIIF consists of subunits TFIIF-α (RAP74) and TFIIF-β (RAP30). It is involved in the stabilization of Pol II association with the PIC and selection of the transcription start site during transcription initiation (1,2). In addition to its role in transcription initiation, TFIIF has been shown to stimulate the transcription elongation activity of Pol II as well as dephosphorylation and recycling of Pol II during transcription termination (3-5).

$303
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Autophagy is a catabolic process for the autophagosomic-lysosomal degradation of proteins activated in response to nutrient deprivation and in neurodegenerative conditions (1). One of the proteins critical to this process is Beclin-1, the mammalian orthologue of the yeast autophagy protein Apg6/Vps30 (2). Beclin-1 can complement defects in yeast autophagy caused by loss of Apg6 and can also stimulate autophagy when overexpressed in mammalian cells (3). Mammalian Beclin-1 was originally isolated in a yeast two-hybrid screen for Bcl-2 interacting proteins and has been shown to interact with Bcl-2 and Bcl-xL, but not with Bax or Bak (4). While Beclin-1 is generally ubiquitously expressed, research studies have shown it is monoallelically deleted in 40-75% of sporadic human breast and ovarian cancers (5). Beclin-1 is localized within cytoplasmic structures including the mitochondria, although overexpression of Beclin-1 reveals some nuclear staining and CRM1-dependent nuclear export (6). Investigators have demonstrated that Beclin-1-/- mice die early in embryogenesis and Beclin-1-/+ mice have a high incidence of spontaneous tumors. Stem cells from the null mice demonstrate an altered autophagic response, although responses to apoptosis appeared normal (7). Researchers have also found that overexpression of Beclin-1 in virally infected neurons in vivo resulted in significant protection against Sindbis virus-induced disease and neuronal apoptosis (4).

$303
100 µl
APPLICATIONS
REACTIVITY
Mouse, Rat

Application Methods: 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).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: 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).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Autophagy is a catabolic process for the autophagosomic-lysosomal degradation of proteins activated in response to nutrient deprivation and in neurodegenerative conditions (1). One of the proteins critical to this process is Beclin-1, the mammalian orthologue of the yeast autophagy protein Apg6/Vps30 (2). Beclin-1 can complement defects in yeast autophagy caused by loss of Apg6 and can also stimulate autophagy when overexpressed in mammalian cells (3). Mammalian Beclin-1 was originally isolated in a yeast two-hybrid screen for Bcl-2 interacting proteins and has been shown to interact with Bcl-2 and Bcl-xL, but not with Bax or Bak (4). While Beclin-1 is generally ubiquitously expressed, research studies have shown it is monoallelically deleted in 40-75% of sporadic human breast and ovarian cancers (5). Beclin-1 is localized within cytoplasmic structures including the mitochondria, although overexpression of Beclin-1 reveals some nuclear staining and CRM1-dependent nuclear export (6). Investigators have demonstrated that Beclin-1-/- mice die early in embryogenesis and Beclin-1-/+ mice have a high incidence of spontaneous tumors. Stem cells from the null mice demonstrate an altered autophagic response, although responses to apoptosis appeared normal (7). Researchers have also found that overexpression of Beclin-1 in virally infected neurons in vivo resulted in significant protection against Sindbis virus-induced disease and neuronal apoptosis (4).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: The process of SUMO conjugation to target proteins is similar to the molecular chain of events observed with ubiquitin (1). SUMO is conjugated to target proteins through the coordinated action of the cellular SUMO conjugation machinery consisting of E1, E2, and E3 enzymes (2). The canonical SUMO E1 activating enzyme is a heterodimer consisting of SAE1 (AOS1) and UBA2 (SAE2) subunits. Mature SUMO is activated by E1 in an ATP-dependent reaction that generates adenylated SUMO, which functions as a high-energy intermediate in the formation of a thioester linkage between SUMO and Cys173 of UBA2 (3,4). SUMO is subsequently transferred from UBA2 to the SUMO E2 conjugating enzyme, UBC9 (5). Recent evidence suggests that redox regulation of UBA2 serves as a physiologic mechanism to modulate the cellular level of sumoylated target proteins (6).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

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, 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, Monkey

Application Methods: Immunoprecipitation, Western Blotting

Background: The process of SUMO conjugation to target proteins is similar to the molecular chain of events observed with ubiquitin (1). SUMO is conjugated to target proteins through the coordinated action of the cellular SUMO conjugation machinery, which consists of the E1, E2, and E3 enzymes (2). The canonical SUMO E1 activating enzyme is a heterodimer consisting of Ubiquitin-like 1-activating enzyme E1A (UBLE1A, SAE1) and UBLE1B (SAE2, UBA2) subunits. Mature SUMO is activated by E1 in an ATP-dependent reaction that generates adenylated SUMO, which functions as a high-energy intermediate in the formation of a thioester linkage between SUMO and Cys173 of SAE2 (3,4). SUMO is subsequently transferred from SAE2 to the SUMO E2 conjugating enzyme UBE2I (5). Research studies indicate that UBLE1A (SAE1) is a nuclear protein and c-Myc transcriptional target whose expression is required for Myc-driven tumorigenesis (6-8).

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

Application Methods: Western Blotting

Background: Ring1A plays a role in polycomb group (PcG) protein function. PcG proteins are critically involved in transcriptional repression of Hox genes during development (1,2). PcG proteins form two distinct complexes: EED-EZH2 and the PRC complex, which is composed of at least Bmi1 and Ring1A/Ring1B. The EZH2-containing complex is responsible for the methylation of H3K27, and the PRC complex ubiquitylates H2A. EZH2 methylation is required prior to PRC ubiquitylation, and both are essential for Hox gene repression (3). It has recently been shown that PcG proteins silence a group of developmentally important regulator genes, referred to as bivalent genes (4). This regulation may be responsible for the ability of stem cells to self renew or switch to differentiate into multipotent progenitors. Aberrant epigenetic silencing by PcG proteins is also thought to be important in tumorigenesis (5).

$303
100 µl
APPLICATIONS
REACTIVITY
Human, Rat

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, Monkey, Mouse, Rat

Application Methods: Western Blotting

Background: Annexin V, also known as PAP-1 or Lipocortin V, is a ~30 kDa protein that binds to phospholipids in a calcium-dependent manner (1). All annexins contain a putative PKC binding site, but only annexin V has been identified as an inhibitor of this pathway (2). It may also signal, by direct interaction with VEGFR2 receptor, in the regulation of vascular endothelial cell proliferation (3). Annexin V preferentially binds phosphatidylserine, in competition with prothrombin, leading to inhibition of blood coagulation at sites of injury preceding contact between lipid components and coagulation factors that initiate thrombosis (4-6). The ability of Annexin V to bind specifically and robustly to phosphatidylserine makes it an attractive reagent in detecting apoptotic cells (7). Annexin V is inducible by glucocorticoids and can be phosphorylated by tyrosine and serine/threonine kinases (8). It is thought to block production of mediators of inflammation, such as prostaglandins and leukotrienes by inhibiting the release of arachidonic acid from membranes by phospholipase A2 (8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

Application Methods: Immunoprecipitation, Western Blotting

Background: Wiskott-Aldrich syndrome proteins (WASPs) mediate actin dynamics by activating the Arp2/3 actin nucleation complex in response to activated Rho family GTPases. In mammals, five WASP family members have been described. Hematopoietic WASP and ubiquitously expressed N-WASP are autoinhibited in unstimulated cells. Upon stimulation they are activated by cdc42, which relieves the autoinhibition in conjunction with phosphatidyl inositol 4,5-bisphosphate. Three WAVE (Wasf, SCAR) family proteins are similar in sequence to WASP and N-WASP but lack the WASP/N-WASP autoinhibition domains and are indirectly activated by Rac (reviewed in 1). Both WASP and WAVE functions appear to be essential, as knockout of either N-WASP or Scar-2 in mice results in cardiac and neuronal defects and embryonic lethality (2,3). Loss of WASP results in immune system defects and fewer immune cells (4). WAVE-2 (WASF2) is widely distributed, while WAVE-1 and WAVE-3 are strongly expressed in brain (5). WAVE-3 may act as a tumor suppressor in neuroblastoma, a childhood disease of the sympathetic nervous system (6). Increased expression of WAVE-3 is seen in breast cancer, and studies in breast adenocarcinoma cells indicate that WAVE-3 regulates breast cancer progression, invasion and metastasis through the p38 mitogen-activated protein kinase (MAPK) pathway (7,8).