mitogen-activated protein kinase activated protein kinase 2

Dual specificity mitogen-activated protein kinase kinase 2, also known as MAP kinase kinase 2, MAPKK2, ERK activator kinase 2, MAPK ERK kinase 2, MEK2 and MAP2K2, is a member of the protein kinase superfamily, STE Ser Thr protein kinase family and MAP kinase kinase subfamily. MAP2K2 MEK2 contains one protein kinase domain. MEK1 and MEK2 (also known as MAP2K1 and MAP2K2, respectively) are evolutionarily conserved, dual-specificity kinases that mediate Erk1 and Erk2 activation during adhesion and growth factor signaling. MAP2K1 MEK1 is a crucial modulator of Mek and Erk signaling and have potential implications for the role of MEK1 and MEK2 in tumorigenesis. MAP2K2 MEK2 catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in a Thr-Glu-Tyr sequence located in MAP kinases. It also activates the ERK1 and ERK2 MAP kinases. Defects in MAP2K2 are a cause of Cardiofaciocutaneous Syndrome (CFC Syndrome) which is characterized by a distinctive facial appearance, heart defects, and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects, and hypertrophic cardiomyopathy.Cancer ImmunotherapyImmune CheckpointImmunotherapyTargeted Therapy

ERK2 Protein, Human, Recombinant (GST) is expressed in Baculovirus insect cells with GST tag. The predicted molecular weight is 67 kDa and the accession number is P28482-1.

Adapter required to activate the JNK and NF-kappa-B signaling pathways through the specific recognition of 'Lys-63'-linked polyubiquitin chains by its RanBP2-type zinc finger (NZF). Acts as an adapter linking MAP3K7 TAK1 and TRAF6 to 'Lys-63'-linked polyubiquitin chains. The RanBP2-type zinc finger (NZF) specifically recognizes Lys-63'-linked polyubiquitin chains unanchored or anchored to the substrate proteins such as RIPK1 RIP1: this acts as a scaffold to organize a large signaling complex to promote autophosphorylation of MAP3K7 TAK1, and subsequent activation of I-kappa-B-kinase (IKK) core complex by MAP3K7 TAK1. Regulates the IL1-mediated translocation of NCOR1 out of the nucleus. Involved in heart development.

Mitogen-activated protein kinase kinase kinase 8, also known as Cancer Osaka thyroid oncogene, Proto-oncogene c-Cot, Serine threonine-protein kinase cot, Tumor progression locus 2 and MAP3K8, is a cytoplasm protein that belongs to the protein kinase superfamily, STE Ser Thr protein kinase family and MAP kinase kinase kinase subfamily. MAP3K8 is expressed in several normal tissues and human tumor-derived cell lines. Isoform 1 of MAP3K8 is activated specifically during the S and G2 M phases of the cell cycle. MAP3K8 is required for TLR4 activation of the MEK ERK pathway. It can activate NF-kappa-B 1 by stimulating proteasome-mediated proteolysis of NF-kappa-B 1 p15. MAP3K8 plays a role in the cell cycle. The longer form has some transforming activity, although it is much weaker than the activated cot oncoprotein. MAP3K8 oncogene linked to human endometrial carcinoma suggesting that it may be another molecule involved in human endometrial cancer. MAP3K8 may also be an important mediator of intracellular mechanotransduction in human bone marrow-derived mesenchymal stem cells (MSCs).

MPK5 Protein, Japonica rice, Recombinant (His & Myc) is expressed in E. coli expression system with N-10xHis and C-Myc tag. The predicted molecular weight is 48.0 kDa and the accession number is Q10N20.

Mitogen-activated protein kinase kinase kinase kinase 2, also known as B lymphocyte serine threonine-protein kinase, Germinal center kinase, MAPK ERK kinase kinase kinase 2, MEK kinase kinase 2, Rab8-interacting protein, and MAP4K2, is cytoplasm and peripheral membrane protein that belongs to the protein kinase superfamily, STE Ser Thr protein kinase family and STE2 subfamily. MAP4K2 contains one CNH domain and one protein kinase domain. Although this kinase is found in many tissues, its expression in lymphoid follicles is restricted to the cells of the germinal center, where it may participate in B-cell differentiation. MAP4K2 can be activated by TNF-alpha and has been shown to specifically activate MAP kinases. It is also found to interact with TNF receptor-associated factor 2 (TRAF2), which is involved in the activation of MAP3K1 MEKK1. MAP4K2 enhances MAP3K1 oligomerization, which may relieve amino-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. It may also play a role in the regulation of vesicle targeting or fusion.

Serine threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1 ERK2 and MAPK3 ERK1 are the 2 MAPKs which play an important role in the MAPK ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG SCF. Depending on the cellular context, the MAPK ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1 RSK1, RPS6KA3 RSK2, RPS6KA2 RSK3, RPS6KA6 RSK4, SYK, MKNK1 MNK1, MKNK2 MNK2, RPS6KA5 MSK1, RPS6KA4 MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade.

ERK2 Protein, Mouse, Recombinant (His & GST) is expressed in Baculovirus insect cells with His and GST tag. The predicted molecular weight is 69.1 kDa and the accession number is P63085.

Dual specificity kinase. Is activated by cytokines and environmental stress in vivo. Catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinase p38. Part of a signaling cascade that begins with the activation of the adrenergic receptor ADRA1B and leads to the activation of MAPK14. MAP2K3 Protein, Human, Recombinant (His & SUMO) is expressed in E. coli expression system with N-6xHis-SUMO tag. The predicted molecular weight is 55.3 kDa and the accession number is P46734.

Mitogen-activated protein kinase 8 (MAPK8), also known as JNK1, is a member of the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. The protein kinases JNK1 has been found to serve as critical molecular links between obesity, metabolic inflammation, and disorders of glucose homeostasis. It is critically involved in the promotion of diet-induced obesity, metabolic inflammation, and beta-cell dysfunction. The selective deficiency of JNK1 in the murine nervous system is sufficient to suppress diet-induced obesity. Genetic analysis indicates that the effects of JNK1 can be separated from the effects of JNK1 on obesity. JNK1 is a potential pharmacological target for the development of drugs that might be useful for the treatment of metabolic syndrome, and type 2 diabetes. Furthermore, JNK1 plays a major role in hypoxic cellular damage. JNK1 protein might be an attractive target for anti-hypoxic therapy in increasing resistance to many pathological conditions and diseases, leading to the oxygen deficit.

IL-4 Protein, Mouse, Recombinant is expressed in E. coli expression system. The predicted molecular weight is 13.4 kDa and the accession number is P07750.

M-CSF CSF1 Protein, Mouse, Recombinant is expressed in HEK293 mammalian cells. The predicted molecular weight is 26 kDa and the accession number is P07141-1.

Involved in countering the first line of host defense mechanisms. Specifically inhibits the response of human neutrophils and monocytes to complement anaphylatoxin C5a and formylated peptides, like N-formyl-methionyl-leucyl-phenylalanine (fMLP). Acts by binding directly to the C5a receptor (C5aR) and formylated peptide receptor (FPR), thereby blocking the C5a- and fMLP-induced calcium responses. Prevents phagocytosis of the bacterium. Chemotaxis inhibitory Protein, S. aureus (strain MRSA252), Recombinant (His) is expressed in yeast with N-6xHis tag. The predicted molecular weight is 16.1 kDa and the accession number is Q6GFB3.

R-Spondin 1 RSPO1 Protein, Mouse, Recombinant (His) is expressed in CHO mammalian cells with His tag. The predicted molecular weight is 28.5 kDa and the accession number is B1ASC1.

PLTP Protein, Human, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 54.5 kDa and the accession number is P55058-1.

IL-23 Protein, Mouse, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 58.3 kDa and the accession number is Q9EQ14&P43432.

Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. Its pro-apoptotic activity is activated via its interaction with PPP1R13B ASPP1 or TP53BP2 ASPP2. However, this activity is inhibited when the interaction with PPP1R13B ASPP1 or TP53BP2 ASPP2 is displaced by PPP1R13L iASPP. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; the function is largely independent of transcription. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis, but seems to have to effect on cell-cycle regulation. Regulates the circadian clock by repressing CLOCK-ARNTL BMAL1-mediated transcriptional activation of PER2.

IL-8 CXCL8 Protein, Human, Recombinant (aa 28-99) is expressed in E. coli expression system. The predicted molecular weight is 8.5 kDa and the accession number is A0A024RDA5.

Dual specific phosphatase 14 MAP-kinase phophatase-6 (DUSP14 MKP6) is a member of Dual-specificity phosphatases that is a subclass of protein tyrosine phosphatases (PTP) families that can dephosphorylate bothe phosphotyrosine and phosphoserine phosphothreonine residues in substrates. Unlike many other DUSPs, DUSP14 only contains a catalytic domain within the C-terminal region. In signal transduction, DUSP14 has been considered as negative regulator of the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 1 2 (ERK 1 2) pathway. DUSP14 phosphatase activity has been confirmed to be inhibited by PTP inhibitor Ⅳ. PTP inhibitor binds to the catalytic site of DUSP14. PTP inhibitor Ⅳ effectively and specifically inhibited DUSP14-mediated dephosphorylation of JNK, a member of the mitogen-activated protein kinase (MAPK) family through dephosphorylation of both the Ser Thr and Tyr residues of MAPKs.

Mitogen-activated protein kinase 9 (MAPK9), also well known as c-Jun N-terminal kinase (JNK2), is a member of the MAP kinase subfamily belonging to the protein kinase superfamily. MAPK9 responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating some transcription factors, such as c-Jun and ATF2. The crystal structure of human JNK2 complexed with an indazole inhibitor by applying a high-throughput protein engineering and surface-site mutagenesis approach. A novel conformation of the activation loop is observed, which is not compatible with its phosphorylation by upstream kinases. This activation inhibitory conformation of JNK2 is stabilized by the MAP kinase insert that interacts with the activation loop in an induced-fit manner. It suggests that the MAP kinase insert of JNK2 plays a role in the regulation of JNK2 activation, possibly by interacting with intracellular binding partners. JNK2 deficiency leads to reduced c-Jun degradation, thereby augmenting c-Jun levels and cellular proliferation, and suggests that JNK2 is a negative regulator of cellular proliferation in multiple cell types. JNK2 prevents replicative stress by coordinating cell cycle progression and DNA damage repair mechanisms. JNK2 blocks the ubiquitination of tumor suppressor p53, and thus increases the stability of p53 in nonstressed cells. JNK2 negatively regulates antigen-specific CD8+ T cell expansion and effector function, and thus selectively blocking JNK2 in CD8+ T cells may potentially enhance the anti-tumor immune response. Lack of JNK2 expression was associated with higher tumor aneuploidy and reduced DNA damage response. Additionally, the JNK2 protein could be a novel therapeutic target in dry eye disease and may provide a novel target for the prevention of vascular disease and atherosclerosis.

Midkine (MK or MDK) also known as neurite growth-promoting factor 2 (NEGF2) is a basic heparin-binding growth factor of low molecular weight, and forms a family with pleiotrophin. Midkine is a retinoic acid-responsive, heparin-binding growth factor expressed in various cell types during embryogenesis. It promotes angiogenesis, cell growth, and cell migration. Midkine is also expressed in several carcinomas, suggesting that it may play a role in tumorigenesis, perhaps through its effects on angiogenesis. Midkine binds anaplastic lymphoma kinase (ALK) which induces ALK activation and subsequent phosphorylation of the insulin receptor substrate (IRS1), followed by the activation of mitogen-activated protein kinase (MAPK) and PI3-kinase and the induction of cell proliferation. Midkine is involved in neointima formation after arterial injury, possibly by mediating leukocyte recruitment. Also involved in early fetal adrenal gland development. Midkine exhibited increased expression in the breast carcinomas but showed much lower expression in the normal breast tissue. Thus, it can be used as a breast carcinomas marker.

MAPK14 contains 1 protein kinase domain and belongs to the MAP kinase family. MAP kinases act as an integration point for multiple biochemical signals and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation, and development. MAPK14 can be detected in the brain, heart, placenta, pancreas, and skeletal muscle and it is expressed to a lesser extent in the lung, liver, and kidney. MAPK14 is activated by various environmental stresses and proinflammatory cytokines. The activation requires its phosphorylation by MAP kinase kinases (MKKs), or its autophosphorylation triggered by the interaction of MAP3K7IP1 TAB1 protein with MAPK14. The substrates of p38 alpha include transcription regulator ATF2, MEF2C, and MAX, cell cycle regulator CDC25B, and tumor suppressor p53, which suggest the roles of p38 alpha in stress-related transcription and cell cycle regulation, as well as in genotoxic stress response. In response to activation by environmental stress, pro-inflammatory cytokines, and lipopolysaccharide, MAPK14 phosphorylates some transcription factors, such as ELK1 and ATF2, and several downstream kinases, such as MAPKAPK2 and MAPKAPK5. MAPK14 plays a critical role in the production of some cytokines, for example, IL-6. It may play a role in the stabilization of EPO mRNA during hypoxic stress. Isoform Mxi2 activation is stimulated by mitogens and oxidative stress and only poorly phosphorylates ELK1 and ATF2.

Ragulator complex protein LAMTOR2, also known as Endosomal adaptor protein p14, Late endosomal lysosomal Mp1-interacting protein, Late endosomal lysosomal adaptor and MAPK and MTOR activator 2, Mitogen-activated protein-binding protein-interacting protein, Roadblock domain-containing protein 3, LAMTOR2, MAPBPIP, and ROBLD3, is a protein which belongs to the GAMAD family. LAMTOR2 ROBLD3 is a regulator of the TOR pathway, a signaling cascade that promotes cell growth in response to growth factors, energy levels, and amino acids. As part of the Ragulator complex, LAMTOR2 ROBLD3 recruits the Rag GTPases and the mTORC1 complex to lysosomes, a key step in the activation of the TOR signaling cascade by amino acids. LAMTOR2 ROBLD3 is an adapter protein that enhances the efficiency of the MAP kinase cascade facilitating the activation of MAPK2. Defects in LAMTOR2 are the cause of immunodeficiency due to defects in MAPBP-interacting protein (ID-MAPBPIP). This form of primary immunodeficiency syndrome includes congenital neutropenia, partial albinism, short stature, and B-cell and cytotoxic T-cell deficiency.

Biliverdin reductase (hBVR) is a serine threonine kinase that catalyzes reduction of the heme oxygenase (HO) activity product, biliverdin, to bilirubin. BVR consists of an N-terminal dinucleotide-binding domain (Rossmann-fold) and a C-terminal domain that contains a six-stranded β-sheet that is flanked on one face by several α-helices. The C-terminal and N-terminal domains interact extensively, forming the active site cleft at their interface. Biliverdin reductase (BVR) catalyzes the last step in heme degradation by reducing the γ-methene bridge of the open tetrapyrrole, biliverdin IXα, to bilirubin with the concomitant oxidation of a β-nicotinamide adenine dinucleotide (NADH) or β-nicotinamide adenine dinucleotide phosphate (NADPH) cofactor. It is now recognized that human BVR (hBVR) is a dual-specificity kinase (Ser Thr and Tyr) upstream activator of the insulin insulin growth factor-1 (IGF-1) and mitogen-activated protein kinase (MAPK) signaling pathways. Human BVR (hBVR) is essential for MAPK-extracellular signal-regulated kinase (ERK)1 2 (MEK)-eukaryotic-like protein kinase (Elk) signaling and has been identified as the cytoplasm-nuclear heme transporter of ERK1 2 and hematin, the key components of stress-responsive gene expression.

Serine threonine-protein kinase 1, also known as Lymphocyte-oriented kinase, STK1 and LOK, belongs to the protein kinase superfamily, STE Ser Thr protein kinase family and STE2 subfamily. Protein kinases constitute a large superfamily of enzymes with key regulatory functions in nearly all signal transmission processes of eukaryotic cells. The Ste2 family of serine threonine kinases plays an important role in numerous cellular functions such as growth, apoptosis, and morphogenesis. STK1 is similar to several known polo-like kinase kinases. It can associate with and phosphorylate polo-like kinase 1, and overexpression of a kinase-dead version of the protein interferes with normal cell cycle progression. STK1 can also negatively regulate interleukin 2 expression in T-cells via the mitogen activated protein kinase kinase 1 pathway. Stk1 can associate with Plk1 in cells and furthermore can phosphorylate Plk1. It can also act on substrates such as myelin basic protein and histone 2A on serine and threonine residues.

FGF (fibroblast growth factor) signalling is known to be required for many aspects of mesoderm formation and patterning during Xenopus development and has been implicated in regulating genes required for the specification of both blood and skeletal muscle lineages. Fibroblast growth factor 4 (FGF4) signaling induces differentiation from embryonic stem cells (ESCs) via the phosphorylation of downstream molecules such as mitogen-activated protein kinase extracellular signal-related kinase (MEK) and extracellular signal-related kinase 1 2 (ERK1 2). Fibroblast Growth Factor 4 (FGF-4) could not only increase the proliferation of bone marrow mesenchymal stem cells (BMSCs), but also induce BMSCs into hepatocyte-like cells in vitro. FGF4 transduced BMSCs contributed to liver regeneration might by the transplanted microenvironment. The FGF4-bFGF BMSCs thus can enhance the survival of the transplanted cells, diminish myocardial fibrosis, promote myocardial angiogenesis, and improve cardiac functions.

CD5 Protein, Mouse, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 39.4 kDa and the accession number is P13379.

GFR Alpha-1 GFRA1 Protein, Human, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 46 kDa and the accession number is P56159-2.

BMP-4 Protein, Human, Recombinant (E399D) is expressed in E. coli expression system. The predicted molecular weight is 13.25 kDa and the accession number is P12644.

Influenza A H2N2 (A Japan 305 1957) Hemagglutinin HA Protein (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 59 kDa and the accession number is P03451.

IL-18R alpha Protein, Mouse, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 36.8 kDa and the accession number is Q61098.

PLA A2 Protein, London plane tree, Recombinant is expressed in HEK293 mammalian cells. The predicted molecular weight is 40.2 kDa.

HVEM Protein, Mouse, Recombinant (His & hFc) is expressed in HEK293 mammalian cells with His and hFc tag. The predicted molecular weight is 46.4 kDa and the accession number is Q80WM9.

EphA4 Protein, Human, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 60 kDa and the accession number is A1MA61.

Nogo Receptor RTN4R Protein, Mouse, Recombinant (His & hFc) is expressed in HEK293 mammalian cells with His and hFc tag. The predicted molecular weight is 73.8 kDa and the accession number is Q99PI8.

Influenza A H10N3 (A duck Hong Kong 786 1979) Hemagglutinin HA1 Protein (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 36.7 kDa and the accession number is A2V811.

SLAM CD150 Protein, Human, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 25.8 kDa and the accession number is Q13291-1.

TIM-1 KIM-1 HAVCR1 Protein, Rat, Recombinant (His & hFc) is expressed in HEK293 mammalian cells with hHis and Fc tag. The predicted molecular weight is 52.6 kDa and the accession number is O54947.

Influenza A H1N1 (A New York 18 2009) Hemagglutinin HA Protein (His) is expressed in Baculovirus insect cells with His tag. The predicted molecular weight is 59 kDa and the accession number is C3W6C4.

BTN3A1 Protein, Human, Recombinant (hFc) is expressed in HEK293 mammalian cells with hFc tag. The predicted molecular weight is 50.9 kDa and the accession number is O00481-2.

SARS-CoV-2 XBB.1.16 (Omicron) Spike RBD Protein (aa 319-529, His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 25.23 kDa and the accession number is YP_009724390.1.

IL-18R beta IL-18RAP Protein, Human, Recombinant (hFc) is expressed in HEK293 mammalian cells with hFc tag. The predicted molecular weight is 65.2 kDa and the accession number is O95256-1.

ESAM Protein, Human, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 25.4 kDa and the accession number is Q96AP7-1.

Nectin-2 Protein, Mouse, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 36 kDa and the accession number is P32507-1.

Asp f 22 Protein, Aspergillus Fumigatus, Recombinant is expressed in E. coli expression system. The predicted molecular weight is 48.1 kDa.

Insulin Receptor Protein, Human, Recombinant (short isoform, His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 106 kDa and the accession number is P06213-2.

CD155 PVR Protein, Human, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 36.5 kDa and the accession number is P15151-1.

IL-10R beta IL-10RB Protein, Human, Recombinant (His) is expressed in HEK293 mammalian cells with His tag. The predicted molecular weight is 25 kDa and the accession number is Q08334.