96 results about "Mitogen-activated protein kinase" patented technology

This invention relates to compounds, compositions, and methods useful for modulating mitogen activated protein kinase (MAP kinase) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of MAP kinase gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of MAP kinase genes, such as Jun amino-terminal kinase (e.g., JNK-1, JNK-2), p38 (MAPK 14), ERK (e.g., ERK-1, ERK-2) and / or c-Jun.

Increasing tolerance to butanol in yeast has been accomplished by increasing activity of the cell wall integrity pathway. Yeast with increased expression of SLT2p, a mitogen activated protein kinase of the MAPK module of the cell wall integrity pathway had increased tolerance to isobutanol. These yeast may be used for improved butanol production.

A method of diagnosing Alzheimer's disease in a patient comprises determining whether the phosphorylation level of an indicator protein in cells of the patient after stimulus with an activator compound is abnormally elevated as compared to a basal phosphorylation level, the indicator protein being e.g. Erk1 / 2 and the activator compound being e.g. bradykinin.

The present invention relates to compositions and methods useful in treating diseases and disorders related to protein kinases. In particular, the present invention relates to compositions and methods useful for targeting protein kinases related to mitogen activated protein kinase (MAPK) pathways (e.g., p38 MAPK, JNK, ERK, and upstream and downstream protein kinases) and / or casein kinase (CK) pathways (e.g., CK1δ, and upstream and downstream protein kinases), and diseases and disorders related to MAPK pathways (e.g., p38 MAPK, JNK, ERK, and upstream and downstream protein kinases) and / or CK pathways (e.g., CK1δ, and upstream and downstream protein kinases).

The present invention is used for evaluating the advantages of haliotis discus hannai. A multi-phase HPLC purification system is used to purify anti-inflammatory peptide from abalone (AAIP, abalone anti-inflammatory peptide). In tandem MS analysis, a fragmentation result shows that the amino acid sequence of the AAIP with nitrogen monoxide (NO) inhibitory activity (IC50=55.8[um]M) is Pro-Phe-Asn-Glu-Gly-Thr-Phe-Ala-Ser (1175.2Da). While the anti-inflammatory effect of RAW264.7 macrophages generated by the stimulus of the AAIP to lipopolysaccharides (LPS) is further studied, and the molecular mechanism is elaborated. The result shows that the AAIP peptide inhibits the nitrogen monoxide (NO) generation induced by the LPS through the expression of inducible nitric oxide synthase (iNOS) by a dose-dependent manner, and the gene transcription of pro-inflammatory cytokines is also obviously reduced, wherein the pro-inflammatory cytokines comprise such as interleukin (IL-1 beta), tumor necrosis factors (TNF-beta) and IL-6. In addition, the AAIP obviously inhibits phosphorylation of mitogen-activated protein kinases (MAPK), such as p-p38 and p-JNK. These results indicate that the AAIP inhibits inflammatory response induced by LPS by intercepting the MAPK pathway of the macrophages. Therefore, the AAIP can be applied to therapeutic drugs for inflammations treatment or healthcare food products.

Provided is a composition for reprogramming somatic cells to generate embryonic stem cell-like cells, comprising: a) a Bmi1 (B cell-specific Moloney murine leukemia virus integration site 1) protein or a nucleic acid molecule encoding the Bmi1 protein; and b) at least one low molecular weight substance selected from the group consisting of a set of a MEK / ERK (mitogen-activated protein kinase / extracellular regulated kinase) inhibitor and a GSK (glycogen synthase kinase) inhibitor, a set of a G9a HMTase (G9a histone methyltransferase) inhibitor and a DMNT (DNA methyltransferase) inhibitor, and a histone deacetylase inhibitor. Also, a method is provided for reprogramming somatic cells to generate embryonic stem cell-like cells using the composition. In addition to reducing the number of the reprogramming factors conventionally needed, the composition and method allow the generation of pluripotent embryonic stem cell-like cells which have high potential in the cell therapy of various diseases.

A method is described for inhibiting mitogen activated protein kinase-activated protein kinase-2 in a subject in need of such inhibition, where the method involves administering to the subject a beta-carboline MK-2 inhibiting compound, or a pharmaceutically acceptable salt thereof.

The invention is based upon the discovery that the mitogen-activated protein kinase (MAPK) pathway can increase CA9 expression independently of HIF-1, as well as increasing CA9 expression under HIF-1-dependent pathways initiated by hypoxia or high cell density. Disclosed herein are novel therapeutic methods for treating preneoplastic / neoplastic diseases associated with abnormal MN / CA IX expression, using MAPK pathway inhibitors. Preferably, the MAPK pathway inhibitors are raf kinase inhibitors, particularly the raf kinase inhibitor Sorafenib. Further disclosed are methods for patient therapy selection for MAPK pathway inhibitors, preferably in combination with other cancer therapies, based on detection of abnormal MN / CA9 gene expression in preneoplastic / neoplastic tissues.

The present invention relates to the mitogen-activated protein kinase called MAPK5. The rice MAPK5 gene, its protein and kinase activity were induced by abscisic acid, pathogen infection, wounding, drought, salt and cold temperature. However, suppression of MAPK5 expression and kinase activity in dsRNAi transgenic plants resulted in constitutive expression of pathogenesis-related genes such as PR-1 and PR-10 but enhanced resistance to fungal and bacterial pathogens. In contrast, overexpressed transgenic lines exhibited elevated MAPK5 kinase activity and increased tolerance to drought, salt and cold stresses. This invention provides methods for increasing tolerance to abiotic and biotic stress in plant using MAPK5.

The invention relates to a cloned protein kinase gene of rice related to salt endurance and the application. The protein kinase gene codes a mitogen activating protein kinase (MAP3K), which is the following protein (i) or (ii): the amino acid sequence with SEQ ID NO: 1 in the sequence table; (ii) the protein derived from (i) with the function of controlling salt endurance of plants after replacing, missing or adding a to ten amino acid residues in the amino acid sequences limited by (i). The cloned protein kinase gene of rice related to salt endurance has the advantages that: the experiment proves that using the gene to transform the rice can significantly increase the salt endurance of rice without evidently influencing the normal growth and economic characters of the rice; the protein and the coding gene have important theoretical and practical significance to the improvement of salt endurance and related characters of the plant as well as the study on tolerance mechanism of the plant in adverse circumstances.

The present invention relates to a composition and a method for generating induced pluripotent stem cells using the same Provided is a composition for reprogramming somatic cells to generate embryonic stem cell-like cells, comprising: a) a Bmi1 (B cell-specific Moloney murine leukemia virus integration site 1) protein or a nucleic acid molecule encoding the Bmi1 protein; and b) at least one low molecular weight substance selected from the group consisting of a set of a MEK / ERK (mitogen-activated protein kinase / extracellular regulated kinase) inhibitor and a GSK (glycogen synthase kinase) inhibitor, a set of a G9a HMTase (G9a histone methyltransferase) inhibitor and a DMNT (DNA methyltransferase) inhibitor, and a histone deacetylase inhibitor. Also, a method is provided for reprogramming somatic cells to generate embryonic stem cell-like cells using the composition.

The present invention discloses a kind of rice mitogen-activated protein kinase and its coding gene and application in breeding very high yield rice variety. The kinase protein with one of the following amino acid residue sequence: 1) SEQ ID No. 1 in the sequence list; and 2. the amino acid residue sequence of SEQ ID No. 1 through substitution, deletion or addition of 1-10 amino acid residues and coding rice grain growth related protein. By means of transgenic technology, the present invention improves the effect of OsMAPK6 on grain shape construction to regulate the activity of grain in accumulating matter and reach the aim of increasing rice yield.

The invention discloses an application of cycloicaritin in preparation of an anti-tumor composition. The cycloicaritin disclosed by the invention can effectively inhibit growth and pipe formation of HUVEC (Human Umbilical Vein Endothelial Cells) and cause apoptosis to inhibit migration of the HUVEC, and has a remarkable inhibiting effect on highly activated MAPK (Mitogen-Activated Protein Kinase) pathway and AKT pathway. Through the above mechanism, the composition can effective prevent tumors, and particularly can effectively inhibit growth of liver cancer, breast cancer, lung cancer, cervical cancer and colon cancer.

The invention provides novel means to inhibit the Mitogen Activated Protein Kinases (MAPKs) pathway activated by Ras / Raf complex using GILZ protein related compounds as inhibitors of Raf / Ras-mediated signal transduction. Pharmaceutical compositions containing such compounds are also disclosed.

The invention relates to phenanthrene and dihydrophenanthrene compounds and an application thereof. The phenanthrene or dihydrophenanthrene compounds can effectively inhibit inflammatory factors and also can inhibit NF (nuclear factor)-kappa B and MAPKs (Mitogen Activated Protein Kinase) signal channels. The compounds or medically acceptable salts, solvates, clathrate compounds or prodrugs thereof can be applied to serving as medicines for treating inflammations and also can be applied to serving as medicines for treating NF-kappa B and MAPKs signal channel related diseases.

The invention belongs to the field of plant genetic engineering, and particularly relates to a poncirustrifoliata mitogen-activated protein kinase (PtrMAPK) gene which is obtained from poncirustrifoliata by separation and cloning. The nucleotide sequence of the gene is shown as a sequence table SEQ ID NO:1; the corresponding amino acid sequence of the gene is shown as a sequence table SEQ ID NO:2; and the gene comprises 1128bp of open reading frame, and encodes 375 amino acids, an isoelectric point is 5.51, and predicted molecular weight is 43kD. The PtrMAPK gene is imported into tobacco for functional verification, and the drought resistance capacity of the obtained transgenic tobacco plant can be improved obviously. New gene resources are provided for anti-abiotic stress molecular design and breeding, new genetic resources are provided for implementing green and environment-friendly agriculture, and the development and utilization of the genetic resources contribute to reducing agriculture production cost and achieving environment-friendliness.

The invention provides a rapid detection method for mitogen activated protein kinase 1 (Mitogen Activated protein Kinase Kinase 1, MEK1 / MAPKK1) gene mutation. The rapid detection method is realized by the following steps: designing a pair of wild primers at the two ends of an MEK1 gene mutation site and designing a pair of mutation primers on the mutation site; respectively designing wild primers and mutation types of a No.2 exon (MEK1-E2) and a No.3 exon (MEK1-E3) of MEK1; respectively amplifying a wild type template and a mutation type template by the primers; utilizing the wild primers to carry out PCR (Polymerase Chain Reaction) amplification on the two templates; respectively amplifying corresponding wild target segment and a mutant type target segment; mixing the two segments according to different ratios and distinguishing by using an HRM method. Compared with the other methods, the rapid detection method has the advantages of high specificity, high sensitivity, convenience and portability; the flux is high and the cost of each time is low.

The present invention relates to compositions and methods useful in treating diseases and disorders related to protein kinases. In particular, the present invention relates to compositions and methods useful for targeting protein kinases related to mitogen activated protein kinase (MAPK) pathways (e.g., p38 MAPK, JNK, ERK, and upstream and downstream protein kinases) and / or casein kinase (CK) pathways (e.g., CK1δ, and upstream and downstream protein kinases), and diseases and disorders related to MAPK pathways (e.g., p38 MAPK, JNK, ERK, and upstream and downstream protein kinases) and / or CK pathways (e.g., CK1δ, and upstream and downstream protein kinases).

The invention relates to crystalline molecules or molecular complexes that comprise binding pockets of mitogen activated protein kinase activated protein kinase 2 (MAPKAPK2) or its homologues. The invention also relates to crystals comprising MAPKAPK2. The present invention also relates to a computer comprising a data storage medium encoded with the structural coordinates of MAPKAPK2 binding pockets and methods of using a computer to evaluate the ability of a compound to bind to the molecule or molecular complex. This invention also relates to methods of using the structure coordinates to solve the structure of homologous proteins or protein complexes. In addition, this invention relates to methods of using the structure coordinates to screen for, design and optimize compounds, including agonists and antagonists, which bind to MAPKAPK2 or homologues thereof.

The invention belongs to the technical field of medicines, in particular relates to a physalin A extracting process and medical application thereof, in particular relates to a novel application of physalin A in preparation of an anti-tumor dug and in particular relates to the use of physalin A in treatment of human fibrosarcoma and human malignant melanoma. After process optimization, the extracting rate of physalin A is 0.2133%. Physalin A can be used for inhibiting the growth of various tumor cells, particularly has obvious inhibiting action on the growth of the human fibrosarcoma and human malignant melanoma, but does not inhibit the activities of the human normal cells obviously. The mechanism is that the downstream caspase family-associated protein is activated by activating Fas death receptors, so that the tumor cells are induced to generate apoptosis. Meanwhile, the physalin A can be used for inducing the tumor cells to generate autophagy for achieving autophagy antagonism apoptosis in the HT1080 and the A375-S2 cells; and the p53 protein and the MAPK (Mitogen-Activated Protein Kinase)-familty p38 protein have a key regulation effect. The physalin A can be used for preparing a digestive tract dosage form or a non-digestive tract dosage form, which can be used for treating tumors including the human fibrosarcoma and human malignant melanoma.

The present invention relates to altering the levels of Th2 cytokine production, and in particular, biasing the cytokine expression profile towards Th2 cytokine production through mitogen-activated protein kinase / ERK kinase kinase 1 (MEKK1), the screening of agents that increase Th2 cytokine production, and the treatment of Th1 associated autoimmune diseases in vivo. In one embodiment, the present invention relates to agents including but not limited to reducing the activity of MEKK1, leading to increased levels of Th2 cytokine production.

The invention relates to a rape mitogen-activated protein kinase gene (Mitogen Activated Protein Kinase, MAPK), in particular to a ubiquitous protein in ubiquitous (rape), the ubiquitous protein is an important element in an eucaryon signal transmission network; the protein is closely related to the plant diseases and insect pests resistance of the rape, the nucleotide sequence and amino acid sequence thereof are shown in a sequence table SEQ ID NO:1 and SEQ ID NO:2. The rape mitogen-activated protein kinase gene has the advantages that: the rape mitogen-activated protein kinase gene has obvious guiding function to the application of biopesticide; the gene clone is valuable to a molecule signal channel which discloses chitosan oligosaccharide induction plant defense responses and has important theoretical direction significance to the application of the oligosaccharide biopesticide.

The invention discloses a detection kit for accessorily diagnosing type 2 diabetes. The detection kit comprise a primer used for detecting the single nucleotide polymorphisms of a PDPK1 (Phosphoinositide Dependent Protein Kinase) gene, a GCK (Glucokinase) gene, a PIK3R2 (Phosphoinositide 3-Kinase Regulatory Subunit 2) gene, an MAPK9 (Mitogen Activated Protein Kinase) gene, a CBLC (Cobalamin C) gene, an MKNK2 gene, an FLOT2 gene, a TRIP10 gene and a KRAS gene, and the single nucleotide polymorphisms respectively include rs76318740, rs12702070, rs3736328, rs1363513, rs2965143, rs3810412, rs4795473, rs340141 and rs7311692. According to the detection kit, PCR (Polymerase Chain Reaction) amplification is carried out on the DNA (Deoxyribose Nucleic Acid) of a sample by virtue of the primer of the detection kit, a melting curve of a PCR amplification product is analyzed by using a fluorescent quantitative PCR instrument, then the melting curve is compared with a standard melting curve, and the Tm value of the PCR amplification product is compared, so that a corresponding genotyping result is obtained. The detection kit disclosed by the invention is capable of accessorily detecting and predicting the diabetes of testee and has the advantages of simple detection method, high detection efficiency and high pertinence, thereby promoting the early prevention of the type 2 diabetes and providing the reference for medication treatment.

The invention provides a composition containing miR-124-3P and application thereof in a drug for inducing neuron formation, and belongs to the technical field of central nerve injury repairing. The composition comprises the miR-124-3P and an inducer, wherein the inducer is selected from one or several of a JAK (Janus Kinase) inhibitor, a p38-MAPK (Mitogen-activated Protein Kinase) inhibitor and anadenylate cyclase activator. The time for trans-differentiating reactive astrocyte into neurons by utilizing the composition provided by the invention is short, the steps are simple and convenient, induction components are less, and the composition is economic, effective and convenient.

The present invention provides for methods and compositions for treating cancer. A subject having cancer is administered an interferon and an inhibitor of mitogen-activated protein kinase (MAPK) signaling pathway. The combination of the interferon and the inhibitor of the MAPK pathway produces a synergistic effect on the cancer compared to the effect of the interferon or the inhibitor of the MAPK pathway alone. The activity of the interferon pathway, interferon expression levels and / or interferon locus copy number can be used as biomarkers for treatment of cancer by MAPK pathway inhibitors.

The invention provides a biomarker of saliva exosom protein. The biomarker includes one or multiple selected from keratin, actin, histone, mitogen activated protein kinase 1, calpain 1, myeloperoxidase, matrix metalloprotease-9 and inflammation protein. The above can serves as a biomarker of AD, and is sensitive, effective and atraumatic. The biomarker can detect and predict whether one has AD, ADcan be prevented and alleviated, and the drug intervention condition can be evaluated.

The invention discloses a polypeptide capable of regulating the activity of FGFR2 (Fibroblast Growth Factor Receptor 2). The amino acid sequence of the polypeptide is Asn-Leu-Gly-Gln-Glu-Leu-Ala-Phe-Arg-Val-Pro-Asn. The polypeptide disclosed by the invention can be specifically combined with the FGFR2, plays an obviously regulating role on the activity of the FGFR2, can outstanding inhibit the activity of p-ERK (Phospho-Extracellular Signal-Regulated Kinase) contained in the main downstream signal channel MAPK (Mitogen Activated Protein Kinase) of the FGFR2, has the advantages of low molecular weight, easiness for preparation, controllability in quality, low immunogenicity and the like and has good potential application value in the field of medicines.

The invention relates to a medicament for treating neurodegenerative diseases and particularly relates to an application of chitosan oligosaccharide in preparation of medicaments for preventing and / or treating neurodegenerative diseases, i.e., the chitosan oligosaccharide can be further applied to the medicaments for preventing and / or treating the neurodegenerative diseases. According to the medicament and the application thereof, with lipopolysaccharide (LPS) as an inducing factor and mouse microglia as a research object, a result shows that the chitosan oligosaccharide can remarkably restrict the expression of the activated microglia iNOS (Inducible Nitric Oxide Synthase) in mRNA (Messenger Ribonucleic Acid) and protein level, can restrict the generation of activated microglia NO (Nitric Oxide), can effectively restrict the generation of activated microglia ROS (Reactive Oxygen Species), can effectively restrict the activation of an MAPK (Mitogen Activated Protein Kinase) signal channel caused by LPS, and can effectively restrict the activation of transcription factor NF-kB (Nuclear Factor-Kappa B) and AP-1 (Activator Protein-1).

The invention discloses a culture medium for rat embryonic stem cells. The culture medium comprises basal culture media and additives, wherein the additives comprise differentiation inhibitors and Pluripotin; and moreover, the differentiation inhibitors comprise GSK (Glycogen Synthase Kinase) inhibitors, FGFR (Fibroblast Growth Factor Receptor) inhibitors and MAPK (Mitogen-activated Protein Kinases) inhibitors. The invention also discloses a culture medium kit of the rat embryonic stem cells, a method for culturing the rat embryonic stem cells and applications of the culture medium and the kit, wherein the culture medium kit comprises the basal culture media, the differentiation inhibitors and the Pluripotin. With the adoption of the differentiation inhibitors and the Pluripotin, the culture medium for the rat embryonic stem cells can inhibit the differentiation of the rat embryonic stem cells and can further guarantee the stability of karyotype for reproductive potential.