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Product listing: GCK Antibody, UniProt ID Q12851 #3782 to p56Dok-2 Antibody, UniProt ID O60496 #3914

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

Application Methods: Western Blotting

Background: Germinal center kinase (GCK) is the founding member of the GCK family, a group of serine/threonine kinases homologous to the yeast Ste20 kinase. GCK is activated by TNF and associated with TRAF2 (TNF receptor-associated factor 2) and MEKK1, thereby activating the SAPK/JNK pathway (1,2). GCK does not significantly phosphorylate MEKK1, instead it enhances MEKK1 oligomerization and autophosphorylation (3). GCK binds and activates MLK3, indicating that GCK may have other effectors (3).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: The GRB7 family of adaptor proteins consist of GRB7, GRB10 and GRB14, which all contain an amino-terminal proline-rich SH3 binding domain, followed by PH, PBS, and SH2 domains. Each member of the family has several splice variants (1). It has been reported that GRB10 interacts with many receptor tyrosine kinases (RTKs) as well as downstream signal molecules including Raf, Akt, and Nedd4 (1,2). Although it was originally thought that GRB10 is exclusively phosphorylated at serine residues (3), Src kinase family members have been shown to phosphorylate GRB10 at Tyr67 (4).

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

Application Methods: Western Blotting

Background: Growth factor receptor-binding protein 2 (GRB2) is an adaptor protein that is involved in RTK signal transduction. The SH2 domain of GRB2 binds to tyrosine phosphorylated proteins such as EGFR, IRS-1, Shc and Gab1 (1). The SH3 domain of GRB2 associates with Sos, which stimulates the GTP binding activity of Ras, leading to the activation of the MAP kinase and other signaling pathways. Phosphorylation of Tyr209 of GRB2 by Bcr-Abl and EGFR abolishes its association with Sos and negatively regulates downstream signaling (2).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: HGK (MAP4K4 or mitogen-activated protein kinase kinase kinase kinase 4) is a serine/threonine kinase that belongs to the mammalian STE20/MAP4K kinase family involved in response to environmental stress and cytokines such as TNF-α (1-3). HGK specifically activates the c-Jun N-terminal kinase (JNK) signaling pathway and increases AP-1-mediated transcriptional activity in vivo (1). HGK is broadly expressed in many types of human cancer and cancer cell lines and plays an important role in cell transformation, invasiveness, adhesion and migration (4,5).

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

Application Methods: Western Blotting

Background: The stress-activated protein kinase/Jun-amino-terminal kinase SAPK/JNK is potently and preferentially activated by a variety of environmental stresses including UV and gamma radiation, ceramides, inflammatory cytokines, and in some instances, growth factors and GPCR agonists (1-6). As with the other MAPKs, the core signaling unit is composed of a MAPKKK, typically MEKK1-MEKK4, or by one of the mixed lineage kinases (MLKs), which phosphorylate and activate MKK4/7. Upon activation, MKKs phosphorylate and activate the SAPK/JNK kinase (2). Stress signals are delivered to this cascade by small GTPases of the Rho family (Rac, Rho, cdc42) (3). Both Rac1 and cdc42 mediate the stimulation of MEKKs and MLKs (3). Alternatively, MKK4/7 can be activated in a GTPase-independent mechanism via stimulation of a germinal center kinase (GCK) family member (4). There are three SAPK/JNK genes each of which undergoes alternative splicing, resulting in numerous isoforms (3). SAPK/JNK, when active as a dimer, can translocate to the nucleus and regulate transcription through its effects on c-Jun, ATF-2, and other transcription factors (3,5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

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

Background: JunB is a basic region, leucine zipper (bZIP) transcription factor belonging to the Jun family that includes c-Jun and JunD. Jun family members homodimerize or heterodimerize with Fos and ATF proteins to form a functional transcription factor AP-1 (activator protein 1), whose activity is regulated by a variety of physiological and pathological stimuli such as growth factors, infections, and stress signals (1-4). While JunB sometimes antagonizes c-Jun transcriptional activity, it may functionally substitute for c-Jun during development in mice (5-7). JunB regulates hematopoietic stem cell number and plays an important role in the pathogenesis of chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) (8,9).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse

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

Background: JunB is a basic region, leucine zipper (bZIP) transcription factor belonging to the Jun family that includes c-Jun and JunD. Jun family members homodimerize or heterodimerize with Fos and ATF proteins to form a functional transcription factor AP-1 (activator protein 1), whose activity is regulated by a variety of physiological and pathological stimuli such as growth factors, infections, and stress signals (1-4). While JunB sometimes antagonizes c-Jun transcriptional activity, it may functionally substitute for c-Jun during development in mice (5-7). JunB regulates hematopoietic stem cell number and plays an important role in the pathogenesis of chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) (8,9).

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

Application Methods: Western Blotting

Background: KSR1 (kinase supressor of Ras) was identified from a genetic screen in Drosophila and C. elegans as a component of the Ras signaling pathway (1). KSR1 has a putative carboxy-terminal kinase domain that lacks a key Lys residue for phospho-group transfer. Although reports indicate that ceramide and EGF activate KSR1 (2,3), other evidence demonstrates that KSR1 regulates Raf in a kinase-independent manner (4,5). It is now widely accepted that KSR1 functions as a scaffold that binds MEK1/2 and 14-3-3 protein constitutively and binds ERK1/2 in a Ras activation-dependent manner (1,5,6). HSP70/HSP90 and p50 Cdc37 associate with the KSR1 complex to ensure its stability (5). Multiple phosphorylation sites have been identified: Ser297 and Ser392 mediate 14-3-3 binding, and putative MAPK phosphorylation sites include Thr260, Thr274 and Ser443 (6). C-TAK1 (Cdc25C-associated kinase 1) binds and phosphorylates KSR1 at Ser392 in quiescent cells (7). In response to stimuli, Ser392 is dephosphorylated by PP2A, which leads to ERK1/2 association and allows the KSR1 complex to translocate from cytosol to membrane, where the MAPK pathway is activated (8). IMP, a Ras-responsive E3 ubiquitin ligase, is also involved in interaction with KSR1 and may regulate its localization and stability (9). Very high expression levels of KSR1 inhibit MAPK signaling, whereas physiological levels promote MAPK signaling, indicating that the scaffold protein can turn signaling "on" or "off" depending on the scaffold concentration (10).

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

Application Methods: Flow Cytometry, Immunoprecipitation, Western Blotting

Background: In response to cytokines, stress, and chemotactic factors, MAP kinase-activated protein kinase 2 (MAPKAPK-2) is rapidly phosphorylated and activated. It has been shown that MAPKAPK-2 is a direct target of p38 MAPK (1). Multiple residues of MAPKAPK-2 are phosphorylated in vivo in response to stress. However, only four residues (Thr25, Thr222, Ser272, and Thr334) are phosphorylated by p38 MAPK in an in vitro kinase assay (2). Phosphorylation at Thr222, Ser272, and Thr334 appears to be essential for the activity of MAPKAPK-2 (2). Thr25 is phosphorylated by p42 MAPK in vitro, but is not required for the activation of MAPKAPK-2 (2).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Monkey, Rat

Application Methods: Western Blotting

Background: MAPKAPK-3 has a single potential SH3-binding site in the proline-rich amino terminus, a putative ATP-binding site, 2 MAP kinase phosphorylation site motifs, and a putative nuclear localization signal. It shares 72% nucleotide and 75% amino acid identity with MAPKAPK-2 (1). MAPKAPK-3 has been shown to be activated by growth inducers and stress stimulation of cells. In vitro studies have demonstrated that Erk, p38 MAP kinase, and Jun amino-terminal kinase are able to phosphorylate and activate MAPKAPK-3, which suggested a role for this kinase as an integrative element of signaling in both mitogen and stress responses (2). MAPKAPK-3 was reported to interact with, phosphorylate, and repress the activity of E47, which is a basic helix-loop-helix transcription factor involved in the regulation of tissue-specific gene expression and cell differentiation (3). MAPKAPK-3 may also support luteal maturation through the phosphorylation and activation of the nuclear transcription factor CREB (4).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: MEF2A is a member of the MEF2 (myocyte enhancer factor 2) family of transcription factors. In mammals, four MEF2A-related genes (MEF2A, MEF2B, MEF2C and MEF2D) encode proteins which exhibit significant amino acid sequence similarity within their DNA binding domains and to a lesser extent throughout the remaining proteins (1). The MEF2 family members were originally described as muscle-specific DNA binding proteins that recognize MEF2 motifs found within the promoters of many muscle-specific genes (2,3). Phosphorylation of MEF2A at Thr312 and Thr319 within the transcription activation domain by p38 MAP kinase enhances MEF2A-MEF2D heterodimer-dependent gene expression (4). On the other hand, apoptotic stimuli (e.g. neurotoxic insult) result in CDK5-dependent phosphorylation of MEF2A at Ser408 within the activation domain, inhibiting MEF2A pro-survival function (5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Myocyte enhancer factor 2D (MEF2D) is a member of the MEF2 family of transcription factors. In mammals, there are four MEF2C-related genes (MEF2A, MEF2B, MEF2C, and MEF2D) that encode proteins that exhibit significant amino acid sequence similarity within their DNA binding domains and, to a lesser extent, throughout the rest of the proteins (1). MEF2 proteins contain a highly conserved N-terminal MADS-box domain, an MEF2 domain, and a more highly variable C-terminal transactivation domain (2). The MEF2 family members were originally described as muscle-specific DNA binding proteins that recognize MEF2 motifs found within the promoters of many muscle-specific genes (3,4); however, more recently they have been found to play critical roles in other physiological processes, such as heart formation and nervous system development (5,6). As such, alterations in MEF2 protein levels can result in developmental and neurological disorders, as well as other diseases such as liver fibrosis and many types of cancer (7). Specifically, MEF2D expression in hepatocellular carcinoma (HCC) is associated with higher levels of proliferation and poor prognosis (8). MEF2D is also overexpressed in clinical colorectal cancer tissues, where its high expression correlates with metastatic process. Functional investigations show that MEF2D promotes cancer cell invasion and epithelial-mesenchymal transition (EMT) and that it is essential for certain microenvironment signals to induce EMT and metastasis in vivo (9). Alternatively, MEF2D may function as a tumor suppressor in lipo- and leiomyosarcoma, as decreased MEF2D activity results in increased cell proliferation and anchorage-independent growth (10). MEF2D may also act as a tumor suppressor in rhabdomyosarcoma, as loss of MEF2D expression results in inhibition of differentiation, increased cell proliferation, and increased anchorage-independent growth (11).

$260
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.

$260
100 µl
$630
300 µl
APPLICATIONS
REACTIVITY
D. melanogaster, Human, Monkey, Mouse, Rat

Application Methods: Immunoprecipitation, 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.

$260
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.

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Immunoprecipitation, Western Blotting

Background: Mitogen-activated protein kinase kinase kinase 2 (MEKK2/MAP3K2) belongs to the MAP3K family of Ser/Thr kinases. Research studies have demonstrated that MEKK2 plays a pivotal role in transducing mitogenic signals emanating from EGFR and FGF2R to JNK and ERK5 signaling cascades (1,2). Post-translationally MEKK2 is regulated through multiple mechanisms including: dimerization (3,4), ubiquitination (5,6), phosphorylation (7) and methylation (8). Research studies implicate dysregulation of MEKK2 signaling in breast carcinoma (9), colorectal carcinoma (10), and pancreatic ductal adenocarcinoma (8).

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Mig6 was identified as a gene which is induced when quiescent fibroblasts are treated by mitogens (1). During cell cycle progression, Mig6 expression levels are also regulated (1). Mig6 mRNA levels were found to increase upon stimulation by chronic stresses including diabetic nephropathy (2). Overexpression of this gene leads to the activation of stress-activated protein kinases (SAPKs)/c-Jun amino-terminal kinases (JNKs) (2). Furthermore, Mig6 was found to interact with epidermal growth factor receptor (EGFR) when stimulated by epidermal growth factor (EGF) (3). Deletion of the Mig6 gene in mice results in hyperactivation of EGFR and signaling through the mitogen-activated protein kinase (MAPK) pathway, causing overproliferation and abnormal differentiation of epidermal keratinocytes in these animals. Inhibition of endogenous EGFR signaling by Iressa abolished skin defects observed in Mig6(-/-) mice, indicating that Mig6 is a specfic negative regulator of EGFR signaling (4). Furthermore, expression of Mig6 was significantly lower in skin, breast, pancreatic and ovarian cancers, suggesting a role of Mig6 as a tumor suppressor (4).

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

Application Methods: Western Blotting

Background: MKK3 and MKK6 are two closely related dual-specificity protein kinases that activate p38 MAP kinase (1-5). MKK3 and MKK6 both phosphorylate and activate p38 MAP kinase at its activation site, Thr-Gly-Tyr, but do not phosphorylate or activate Erk1/2 or SAPK/JNK. Phosphorylation of p38 MAP kinase dramatically stimulates its ability to phosphorylate protein substrates such as ATF-2 and Elk-1. MKK3 and MKK6 are both activated by different forms of cellular stress and inflammatory cytokines (4,5). Activation of MKK3 and MKK6 occurs through phosphorylation at Ser189 and Thr222 on MKK3 (2) and Ser207 and Thr211 on MKK6 (4,5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: MKK3 and MKK6 are two closely related dual-specificity protein kinases that activate p38 MAP kinase (1-5). MKK3 and MKK6 both phosphorylate and activate p38 MAP kinase at its activation site, Thr-Gly-Tyr, but do not phosphorylate or activate Erk1/2 or SAPK/JNK. Phosphorylation of p38 MAP kinase dramatically stimulates its ability to phosphorylate protein substrates such as ATF-2 and Elk-1. MKK3 and MKK6 are both activated by different forms of cellular stress and inflammatory cytokines (4,5). Activation of MKK3 and MKK6 occurs through phosphorylation at Ser189 and Thr222 on MKK3 (2) and Ser207 and Thr211 on MKK6 (4,5).

$260
100 µl
APPLICATIONS
REACTIVITY
Human, Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: MKK3 and MKK6 are two closely related dual-specificity protein kinases that activate p38 MAP kinase (1-5). MKK3 and MKK6 both phosphorylate and activate p38 MAP kinase at its activation site, Thr-Gly-Tyr, but do not phosphorylate or activate Erk1/2 or SAPK/JNK. Phosphorylation of p38 MAP kinase dramatically stimulates its ability to phosphorylate protein substrates such as ATF-2 and Elk-1. MKK3 and MKK6 are both activated by different forms of cellular stress and inflammatory cytokines (4,5). Activation of MKK3 and MKK6 occurs through phosphorylation at Ser189 and Thr222 on MKK3 (2) and Ser207 and Thr211 on MKK6 (4,5).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: MKK7 is a MAP kinase kinase that serves as a specific activator of the SAPK/JNK pathway (1,2). MKK7 is strongly activated by TNF-α, as well as other environmental stresses, whereas SEK1/MKK4, which activates both p38 and SAPK/JNK pathways, is not activated by TNF-α (2). Sequence alignment of the activation loop of the MAP kinase kinase family members indicates that Ser271 and Thr275 are potential phosphorylation sites that are crucial for the kinase acivity.

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

Application Methods: Western Blotting

Background: Mixed lineage kinase 3 (MLK3) is a serine/threonine kinase that has an amino-terminal SH3 domain followed by the kinase domain and two leucine zippers, a cdc42/Rac1 binding (CRIB) domain and several other domains/motifs at the carboxy-terminal region. CRIB triggers the dimerization of MLK3 via its tandem leucine zippers, followed by the intramolecular phosphorylation and subsequent activation of MLK3 (1,2). Autophosphorylation of Thr277 and Ser281 is essential for MLK3 kinase activity (3). Ser281 is also phosphorylated by HPK in an in vitro kinase assay (3). MLK3 functions as a MAPKKK of the SAPK/JNK stress pathway by directly phosphorylating SEK1/MKK4 and MKK7, although it is controversial whether MLK3 is involved in p38 stress pathway activation (1,4). MLK3 also functions as an IκB kinase and mediates the activation of the transcriptional factor NF-κB stimulated by CD3/CD28, suggesting a role for MLK3 in immune and inflammatory responses (5).

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

Application Methods: Western Blotting

Background: The Src family of protein tyrosine kinases, which includes Src, Lyn, Fyn, Yes, Lck, Blk, and Hck, are important in the regulation of growth and differentiation of eukaryotic cells (1). Src activity is regulated by tyrosine phosphorylation at two sites, but with opposing effects. While phosphorylation at Tyr416 in the activation loop of the kinase domain upregulates enzyme activity, phosphorylation at Tyr527 in the carboxy-terminal tail by Csk renders the enzyme less active (2).

$260
200 µl
$630
600 µl
APPLICATIONS
REACTIVITY
Guinea Pig, Human, Monkey, Mouse, Rat

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

Background: p38 MAP kinase (MAPK), also called RK (1) or CSBP (2), is the mammalian orthologue of the yeast HOG kinase that participates in a signaling cascade controlling cellular responses to cytokines and stress (1-4). Four isoforms of p38 MAPK, p38α, β, γ (also known as Erk6 or SAPK3), and δ (also known as SAPK4) have been identified. Similar to the SAPK/JNK pathway, p38 MAPK is activated by a variety of cellular stresses including osmotic shock, inflammatory cytokines, lipopolysaccharide (LPS), UV light, and growth factors (1-5). MKK3, MKK6, and SEK activate p38 MAPK by phosphorylation at Thr180 and Tyr182. Activated p38 MAPK has been shown to phosphorylate and activate MAPKAP kinase 2 (3) and to phosphorylate the transcription factors ATF-2 (5), Max (6), and MEF2 (5-8). SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-imidazole) is a selective inhibitor of p38 MAPK. This compound inhibits the activation of MAPKAPK-2 by p38 MAPK and subsequent phosphorylation of HSP27 (9). SB203580 inhibits p38 MAPK catalytic activity by binding to the ATP-binding pocket, but does not inhibit phosphorylation of p38 MAPK by upstream kinases (10).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: p38 MAP kinase (MAPK), also called RK (1) or CSBP (2), is the mammalian orthologue of the yeast HOG kinase that participates in a signaling cascade controlling cellular responses to cytokines and stress (1-4). Four isoforms of p38 MAPK, p38α, β, γ (also known as Erk6 or SAPK3), and δ (also known as SAPK4) have been identified. Similar to the SAPK/JNK pathway, p38 MAPK is activated by a variety of cellular stresses including osmotic shock, inflammatory cytokines, lipopolysaccharide (LPS), UV light, and growth factors (1-5). MKK3, MKK6, and SEK activate p38 MAPK by phosphorylation at Thr180 and Tyr182. Activated p38 MAPK has been shown to phosphorylate and activate MAPKAP kinase 2 (3) and to phosphorylate the transcription factors ATF-2 (5), Max (6), and MEF2 (5-8). SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-imidazole) is a selective inhibitor of p38 MAPK. This compound inhibits the activation of MAPKAPK-2 by p38 MAPK and subsequent phosphorylation of HSP27 (9). SB203580 inhibits p38 MAPK catalytic activity by binding to the ATP-binding pocket, but does not inhibit phosphorylation of p38 MAPK by upstream kinases (10).

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

Application Methods: Immunoprecipitation, Western Blotting

Background: p38 MAP kinase (MAPK), also called RK (1) or CSBP (2), is the mammalian orthologue of the yeast HOG kinase that participates in a signaling cascade controlling cellular responses to cytokines and stress (1-4). Four isoforms of p38 MAPK, p38α, β, γ (also known as Erk6 or SAPK3), and δ (also known as SAPK4) have been identified. Similar to the SAPK/JNK pathway, p38 MAPK is activated by a variety of cellular stresses including osmotic shock, inflammatory cytokines, lipopolysaccharide (LPS), UV light, and growth factors (1-5). MKK3, MKK6, and SEK activate p38 MAPK by phosphorylation at Thr180 and Tyr182. Activated p38 MAPK has been shown to phosphorylate and activate MAPKAP kinase 2 (3) and to phosphorylate the transcription factors ATF-2 (5), Max (6), and MEF2 (5-8). SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-imidazole) is a selective inhibitor of p38 MAPK. This compound inhibits the activation of MAPKAPK-2 by p38 MAPK and subsequent phosphorylation of HSP27 (9). SB203580 inhibits p38 MAPK catalytic activity by binding to the ATP-binding pocket, but does not inhibit phosphorylation of p38 MAPK by upstream kinases (10).

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

Application Methods: Western Blotting

Background: Mitogen-activated protein kinases (MAPKs) are a widely conserved family of serine/threonine protein kinases involved in many cellular programs, such as cell proliferation, differentiation, motility, and death. The p44/42 MAPK (Erk1/2) signaling pathway can be activated in response to a diverse range of extracellular stimuli including mitogens, growth factors, and cytokines (1-3), and research investigators consider it an important target in the diagnosis and treatment of cancer (4). Upon stimulation, a sequential three-part protein kinase cascade is initiated, consisting of a MAP kinase kinase kinase (MAPKKK or MAP3K), a MAP kinase kinase (MAPKK or MAP2K), and a MAP kinase (MAPK). Multiple p44/42 MAP3Ks have been identified, including members of the Raf family, as well as Mos and Tpl2/COT. MEK1 and MEK2 are the primary MAPKKs in this pathway (5,6). MEK1 and MEK2 activate p44 and p42 through phosphorylation of activation loop residues Thr202/Tyr204 and Thr185/Tyr187, respectively. Several downstream targets of p44/42 have been identified, including p90RSK (7) and the transcription factor Elk-1 (8,9). p44/42 are negatively regulated by a family of dual-specificity (Thr/Tyr) MAPK phosphatases, known as DUSPs or MKPs (10), along with MEK inhibitors, such as U0126 and PD98059.

$260
100 µl
APPLICATIONS
REACTIVITY
Mouse, Rat

Application Methods: Immunoprecipitation, Western Blotting

Background: Mitogen-activated protein kinases (MAPKs) are a widely conserved family of serine/threonine protein kinases involved in many cellular programs, such as cell proliferation, differentiation, motility, and death. The p44/42 MAPK (Erk1/2) signaling pathway can be activated in response to a diverse range of extracellular stimuli including mitogens, growth factors, and cytokines (1-3), and research investigators consider it an important target in the diagnosis and treatment of cancer (4). Upon stimulation, a sequential three-part protein kinase cascade is initiated, consisting of a MAP kinase kinase kinase (MAPKKK or MAP3K), a MAP kinase kinase (MAPKK or MAP2K), and a MAP kinase (MAPK). Multiple p44/42 MAP3Ks have been identified, including members of the Raf family, as well as Mos and Tpl2/COT. MEK1 and MEK2 are the primary MAPKKs in this pathway (5,6). MEK1 and MEK2 activate p44 and p42 through phosphorylation of activation loop residues Thr202/Tyr204 and Thr185/Tyr187, respectively. Several downstream targets of p44/42 have been identified, including p90RSK (7) and the transcription factor Elk-1 (8,9). p44/42 are negatively regulated by a family of dual-specificity (Thr/Tyr) MAPK phosphatases, known as DUSPs or MKPs (10), along with MEK inhibitors, such as U0126 and PD98059.

$260
200 µl
$630
600 µl
APPLICATIONS
REACTIVITY
Bovine, Hamster, Human, Mink, Monkey, Mouse, Pig, Rat, S. cerevisiae, Zebrafish

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

Background: Mitogen-activated protein kinases (MAPKs) are a widely conserved family of serine/threonine protein kinases involved in many cellular programs, such as cell proliferation, differentiation, motility, and death. The p44/42 MAPK (Erk1/2) signaling pathway can be activated in response to a diverse range of extracellular stimuli including mitogens, growth factors, and cytokines (1-3), and research investigators consider it an important target in the diagnosis and treatment of cancer (4). Upon stimulation, a sequential three-part protein kinase cascade is initiated, consisting of a MAP kinase kinase kinase (MAPKKK or MAP3K), a MAP kinase kinase (MAPKK or MAP2K), and a MAP kinase (MAPK). Multiple p44/42 MAP3Ks have been identified, including members of the Raf family, as well as Mos and Tpl2/COT. MEK1 and MEK2 are the primary MAPKKs in this pathway (5,6). MEK1 and MEK2 activate p44 and p42 through phosphorylation of activation loop residues Thr202/Tyr204 and Thr185/Tyr187, respectively. Several downstream targets of p44/42 have been identified, including p90RSK (7) and the transcription factor Elk-1 (8,9). p44/42 are negatively regulated by a family of dual-specificity (Thr/Tyr) MAPK phosphatases, known as DUSPs or MKPs (10), along with MEK inhibitors, such as U0126 and PD98059.

$260
100 µl
APPLICATIONS
REACTIVITY
Human

Application Methods: Western Blotting

Background: Docking proteins are substrates of tyrosine kinases that function in the recruitment and assembly of specific signal transduction molecules. There are five members in the p62dok family, p62Dok (Dok-1), p56Dok-2 (Dok-2, or DoK-R), Dok-3, Dok-4 and Dok-5 (1-3), characterized by the presence of an amino-terminal PH domain, a central PTB domain and numerous potential sites of tyrosine phosphorylation. Tyrosine phosphorylation of p56Dok-2 occurs upon stimulation of cells with a variety of stimuli, or in cells transformed by oncogenic tyrosine kinases such as v-Src and Bcr-Abl (3-5). Based on the presence of several signaling domains (PH, PTB domain, tyrosine residue and proline-rich regions), it has been proposed that the p62dok family act as docking proteins that link RTKs to signal transduction pathways. p56Dok-2 has been proposed to be a negative regulator of cytokine-induced proliferation in T cells (5). Phosphorylated Tyr351 of p56Dok-2 mediates an association with the SH2 domain of Nck (4).