46 results about "Mitogen activate protein" patented technology

This invention relates to a method for prevention and treatment of aging and age-related disorders including atherosclerosis, peripheral vascular disease, coronary artery disease, osteoporosis, type 2 diabetes, dementia and some forms of arthritis and cancer in a subject comprising administering to said subject, separately, sequentially or simultaneously a therapeutically effective dosage of each component or combination of statins, bisphosphonates, cholesterol lowering agents or techniques, interleukin-6 inhibitor / antibody, interleukin-6 receptor inhibitor / antibody, interleukin-6 antisense oligonucleotide (ASON), gp130 protein inhibitor / antibody, tyrosine kinases inhibitors / antibodies, serine / threonine kinases inhibitors / antibodies, mitogen-activated protein (MAP) kinase inhibitors / antibodies, phosphatidylinositol 3-kinase (PI3K) inhibitors / antibodies, Nuclear factor κB (NF-κB) inhibitors / antibodies, IκB kinase (IKK) inhibitors / antibodies, activator protein-1 (AP-1) inhibitors / antibodies, STAT transcription factors inhibitors / antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, or a functional fragment thereof, administered separately, in sequence or simultaneously. Inhibition of the signal transduction pathway for Interleukin 6 mediated inflammation is key to the prevention and treatment of atherosclerosis, peripheral vascular disease, coronary artery disease, aging and age-related disorders including osteoporosis, type 2 diabetes, dementia and some forms of arthritis and tumors. Inhibition of Interleukin 6 mediated inflammation may be achieved indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion or by direct inhibition of the signal transduction pathway utilizing interleukin-6 inhibitor / antibody, interleukin-6 receptor inhibitor / antibody, interleukin-6 antisense oligonucleotide (ASON), gp130 protein inhibitor / antibody, tyrosine kinases inhibitors / antibodies, serine / threonine kinases inhibitors / antibodies, mitogen-activated protein (MAP) kinase inhibitors / antibodies, phosphatidylinositol 3-kinase (PI3K) inhibitors / antibodies, Nuclear factor κB (NF-κB) inhibitors / antibodies, IκB kinase (IKK) inhibitors / antibodies, activator protein-1 (AP-1) inhibitors / antibodies, STAT transcription factors inhibitors / antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, or a functional fragment thereof. Said method for prevention and treatment of said disorders is based on inhibition of Interleukin-6 inflammation through regulation of cholesterol metabolism, isoprenoid depletion and / or inhibition of the signal transduction pathway.

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.

There is provided a compound of formula I,which compound has antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases, e.g., Src and Lck) and has use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

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.

Methods for enhancing the suppressive function of myeloid derived suppressor cells (MDSCs) for the treatment of autoimmune diseases using small compounds are disclosed. In certain aspects, the small compounds are glatiramer acetate and mitogen activated protein (MAP) kinase inhibitors. In other aspects, these methods include the administration of exogenous MD-SCs or the use of endogenous MDSCs mobilized using stem cell mobilizers. In yet other aspects, compositions containing MDSCs and small compounds of the invention are provided.

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.

Increasing tolerance to butanol in yeast has been accomplished by increasing activity of the high osmolarity / glycerol response pathway. Yeast with increased expression of PBS2p, a mitogen activated protein kinase kinase of the MAPK module of the high osmolarity / glycerol response pathway may be used for improved butanol production.

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.

Methods and compositions for modulating plant response, development and yield under varying environmental conditions are provided. Methods employing MAPKKK are provided. The MAPKKK sequences are used in a variety of methods including modulating root development, modulating leaf and / or shoot development, modulating tolerance under abiotic stress and modulating yield. Transformed plants, plant cell, tissues, seed and expression vectors are also provided.

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 a gene GhMKK5 capable of improving bacterial resistance of transgenic crops and an application thereof, belonging to the fields of molecular biology and biotechnology. According to the invention, a cotton mitogen-activated protein kinase gene GhMKK5 is obtained by the homologous cloning and RACE technology; the cDNA (complementary deoxyribonucleic acid) of the gene is placed under a CaMV 35S starter to construct a plant expression vector; and nicotiana benthamiana is transformed so that the gene is over-expressed in tobacco. Experiments demonstrate that: the transgenic tobacco has obvious capability in resisting bacteriosis. By applying the gene to the crops such as transformed wheat, cotton and the like, the antibacterial capability can be enhanced, the yield and quality can be improved, and tremendous economic and social values can be realized.

The invention relates to clone and recombination of a cotton mitogen activated protein kinase gene as well as salt resistance function analysis and application thereof, belonging to the fields of molecular biology and biotechnology. In the invention, total RNA is extracted from primary leaves of the cotton, and reverse transcription is carried out to obtain obtains cDNA. A degenerate primer is designed according to a conservative amino acid sequence of the mitogen activated protein kinase gene in the other plants to carry out a conventional polymerase chain reaction, a PCR product is connected with a pMD18-T carrier to transform a colibacillus DH5 alpha competent cell, a recombinant is selected to carry out sequence analysis, and the full-length cDNA is obtained through a rapid amplification technology of 3'end and 5' end. A plant positive expression vector is further constructed to transform the tobacco cultivated variety NC89, the transgenic tobacco has the obvious salt resistance capacity so as to transform the gene into crops such as cottons, wheat, corns, and the like, thereby improving the salt resistance capacity of the crops and increasing the yield and the quality of the crops, and having important economy value and social value.

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 invention discloses a radix notoginseng mitogen-activated protein kinase kinase gene PnMAPKK1.A nucleotide sequence of the gene PnMAPKK1 is as shown in SEQ ID NO:1, and the gene PnMAPKK1 codes mitogen-activated protein kinase kinase.According to functional genomics related technical researches, the gene PnMAPKK1 has a function of improving pathogenic fungus resistance of plants.After the antifungal gene PnMAPKK1 is constructed to a plant expression vector and transferred into tobaccos to realize overexpression, transgenic tobacco plants have extremely high in-vitro antifungal activity.The transgenic tobacco plants with PnMAPKK1 overexpressed have an evident inhibition effect on growth of fusarium solani, colletotrichum gloeosporioides, verticillium fusarium and botryosphaeria.

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 invention discloses a breast cancer-related kinase mutation detection panel. The detection panel comprises receptor tyrosine kinase (RTK), phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MAPK) related genes, and an exon region and a part of intronic regions of a downstream gene. The invention further discloses a kit containing the detection panel. The detection panel can detect gene mutation guiding diagnosis and treatment more efficiently, is of great significance to clinical diagnosis and discovery of a target spot of target treatment, and can help lower gene detection cost of patients.

This invention is directed to new inhibitors of the p38 mitogen-activated protein kinase having the general formula (I) to processes for their preparation; to pharmaceutical compositions comprising them; and to their use in therapy.

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.

A new phosphorylation site of mitogen-activated kinase proteins (MAPK) has been found. Phosphorylated MAPKs in said phosphorylation site can be used as a diagnostic marker of pathologies mediated by MAPKs.

Mitogen activated protein kinase (MAPK) inhibitors disclosed herein are useful for the treatment of diseases of the respiratory tract, such as chronic eosinophilic pneumonia, asthma, COPD, adult respiratory distress syndrome (ARDS), exacerbation of airways hyper-reactivity consequent to other drug therapy, and airways disease that is associated with pulmonary hypertension.

The invention relates to new application of a compound, in particular to application in the preparation of a medicament for preventing and controlling lipopolysaccharide (LPS)-induced acute liver damage. A protein kinase D (PKD) inhibitor has the advantages of preventing LPS-induced mice acute liver damage, remarkably reducing the phosphorylation level of LPS-induced PKD, lowering death rate and levels of alanine aminotransferase (ALT) and aspartate transaminase (AST), improving inflammatory reaction, restraining the signal channel of LPS activated p38 mitogen-activated protein kinase (p38MAPK), lowering the level of LPS-induced tumor necrosis factor-alpha (TNK-alpha), reducing the apoptosis number of hepatic cells, the activation of caspases and the expression level of hepatic tissue adhesion molecules and lowering the activation level of myeloperoxidase (MPO).

The invention discloses a Haynaldia villosa mitogen activated protein kinase gene Hv-MPK12 and a protein encoded thereby, and belongs to the field of gene engineering. The cDNA sequence of the Hv-MPK12 is represented by SEQ ID NO.1, and the amino acid sequence encoded thereby is represented by SEQ ID NO.2. The gene is from Haynaldia villosa L. (2n=2x=14, genome VV), and powdery mildew fungus induced expression enhancement of the gene in powdery mildew-resistant Haynaldia villosa L. (2n=2x=14, genome VV) is realized. The gene is transformed to an infected wheat species Yangmai 158, and a result shows that the overexpression of the Hv-MPK12 gene can enhance the wheat powdery mildew resistance of the Yangmai 158. The Hv-MPK12 is expected to be used in gene engineering breeding, and can be introduced in to wheat species susceptible to powdery mildew in order to possibly improve the powdery mildew resistance of wheat.

A method of reducing blood glucose in a subject has been developed. In preferred embodiments, the method involves administering to the subject a specific activator of endogenous mitogen-activated protein kinase kinase 6 (MKK3), mitogen-activated protein kinase kinase 6 (MKK4), mitogen-activated protein kinase kinase 6 (MKK6), p38 mitogen-activated protein kinase (p38MAPK), mitogen-activated kinase-activated protein kinase 2 (MK2), or a combination thereof, in an effective amount to reduce blood glucose in a subject. In other embodiments, the method involves administering to the subject a specific activator to increase X-box binding protein 1 (XBP1) phosphorylation on Thr48 and Ser61 in an effective amount to reduce blood glucose in the subject. Methods of identifying agents for reducing blood glucose in a subject are also provided.

A method of reducing blood glucose in a subject has been developed. In preferred embodiments, the method involves administering to the subject a specific activator of endogenous mitogen-activated protein kinase kinase 6 (MKK3), mitogen-activated protein kinase kinase 6 (MKK4), mitogen-activated protein kinase kinase 6 (MKK6), p38 mitogen-activated protein kinase (p38MAPK), mitogen-activated kinase-activated protein kinase 2 (MK2), or a combination thereof, in an effective amount to reduce blood glucose in a subject. In other embodiments, the method involves administering to the subject a specific activator to increase X-box binding protein 1 (XBP1) phosphorylation on Thr48 and Ser61 in an effective amount to reduce blood glucose in the subject. Methods of identifying agents for reducing blood glucose in a subject are also provided.

Provided herein are pharmaceutical combinations comprising (a) a B-Raf inhibitor, or a pharmaceutically acceptable salt thereof, (b) at least one mitogen activated protein kinase (MEK) inhibitor, or a pharmaceutically acceptable salt thereof, and (c) an epidermal growth factor receptor (EGFR) inhibitor or a pharmaceutically acceptable salt thereof; and optionally at least one pharmaceutically acceptable carrier; methods for preparing the pharmaceutical combinations, and the uses of the pharmaceutical combinations in the treatment of proliferative diseases, such as cancer.

The invention relates to a kit for detecting disease susceptibility. The susceptibility of acute myeloid leukemia is predicted by detecting a single nucleotide polymorphism (SNP) site of mitogen activated protein kinase 4 (CD44). The kit comprises a fluorescence quantitative polymerase chain reaction (PCR) conventional component, a specific primer pair for detecting the No.rs11821102 SNP site of the CD44 and a specific fluorescence probe pair. The kit can detect the gene type of the No.rs11821102 SNP site on the CD44 gene of DNA so as to detect the susceptibility of individual acute myeloid leukemia, is also suitable for prognostic detection of gastric cancer, prostatic cancer and ovarian cancer, and can be widely applied in medicinal research.