90 results about "Tyrosine phosphorylation" patented technology

Permeability of the blood-brain barrier and other physiological barriers can be modulated by the degree of tyrosine phosphorylation of proteins. Agents which promote tyrosine protein dephosphorylation reduce the permeability of the blood-brain barrier and those which promote phosphorylation increase permeability. Increasing blood-brain barrier permeability is useful in delivering drugs having a desired effect upon the central nervous system; decreasing blood-brain barrier permeability and other physiological barrier permeability is useful in preventing undesired compounds reaching the CNS and in certain clinical conditions.

The present invention identifies a protein, designated the D-sequence-binding protein (D-BP), is phosphorylated at tyrosine residues and blocks AAV-mediated transgene expression in infected cells by inhibiting the leading strand viral DNA synthesis. More particularly, the present invention demonstrates that D-BP is phosphorylated by EGF-R protein tyrosine kinase. Methods of increasing transcription and promoting replication of transgenes exploiting this information are disclosed herein.

The present invention describes a therapeutic method useful for treating or preventing a condition of platelet aggregation in a subject including administering a pharmaceutically effective amount of a compound or composition that inhibits JAK-3 and / or tyrosine phosphorylation of STAT-3 and inhibits thrombin induced platelet aggregation. The condition of platelet aggregation includes hematopoietic and cerbrovascular diseases.

An antibody is disclosed for the detection of phosphorylated c-KIT. A method of diagnosing and monitoring cancers responsive to treatment using an anti-phospho-c-KIT antibody are also disclosed. A diagnostic kit is also provided for the detection and monitoring of cancers responsive to tyrosine phosphorylation inhibitor treatment.

Tyrosine phosphorylation, regulated by protein tyrosine phosphatases (PTPs) and kinases (PTKs), is important in signaling pathways underlying tumorigenesis. A mutational analysis of the tyrosine phosphatase gene superfamily in human cancers identified 83 somatic mutations in six PTPs (PTPRF, PTPRG, PTPRT, PTPN3, PTPN13, PTPN14) affecting 26% of colorectal cancers and a smaller fraction of lung, breast and gastric cancers. Fifteen mutations were nonsense, frameshift or splice site alterations predicted to result in truncated proteins lacking phosphatase activity. Five missense mutations in the most commonly altered PTP (PTPRP) were biochemically examined and found to reduce phosphatase activity. Expression of wild-type but not a mutant PTPRT in human cancer cells inhibited cell growth. These observations suggest that the tyrosine phosphatase genes are tumor suppressor genes, regulating cellular pathways that may be amenable to therapeutic intervention.

The invention discloses 482 novel phosphorylation sites identified in carcinoma and / or leukemia, peptides (including AQUA peptides) comprising a phosphorylation site of the invention, antibodies specifically bind to a novel phosphorylation site of the invention, and diagnostic and therapeutic uses of the above.

The invention discloses nearly 474 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human carcinoma, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites / proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: Kinase, Adaptor / Scaffold proteins, Phosphatase, G protein Regulator / Guanine Nucleotide Exchange Factors / GTPase Activating Proteins, Cytoskeleton Proteins, DNA Binding Proteins, Phospholipase, Receptor Proteins, Enzymes, DNA Repair / Replication Proteins, Adhesion Proteins, and Proteases, as well as other protein types.

The invention provides a silk fibroin biological material compounded with the epidermal growth factor and a preparation method of the silk fibroin biological material. Silk fibroin is a natural high polymer material extracted from fibroin of silk, has good biocompatibility, is non-toxic to the body, has no sensitization and stimulation effects, and is partially biodegradable; the epidermal growth factor belongs to active substance in the human body, is peptide active substance composed of 53 amino acid residues, and can stimulate the tyrosine phosphorylation of receptors of the epidermal growth factors, so that the effect of repairing hyperplasia can be achieved, therefore, the silk fibroin biological scaffold prepared by adopting silk fibroin and the epidermal growth factor is degradable, and has the function of promoting the wound healing, and in addition, the operation is simple during the preparation of the silk fibroin biological scaffold.

It has been found out that among antibodies showing reactivity with wild type TGF-α, antibodies less reactive with G79A-substituted TGF-α have an excellent growth-suppressing effect on cancer cells having a mutated Ras gene. Further, it has been found out that most of these antibodies have an activity of inhibiting EGFR tyrosine phosphorylation and / or an induction-suppressing activity on vascular endothelial cells.

The invention discloses nearly 288 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human Leukemia, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites / proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: Adaptor / Scaffold proteins, Cytoskeletal proteins, Cellular Metabolism enzymes, G Protein / GTPase Activating / Guanine Nucleotide Exchange Factor proteins, Immunoglobulin Superfamily proteins, Inhibitor proteins, Lipid Kinases, Nuclear DNA Repair / RNA Binding / Transcription proteins, Serine / Threonine Protein Kinases, Tyrosine Kinases, Protein Phosphatases, and Translation / Transporter proteins.

The invention discloses 443 novel phosphorylation sites identified in leukemia, peptides (including AQUA peptides) comprising a phosphorylation site of the invention, antibodies specifically bind to a novel phosphorylation site of the invention, and diagnostic and therapeutic uses of the above.

The invention discloses a preparation method for a fluorescent molecular imprinted probe. Cadmium telluride quantum dots are taken as a fluorescent element, and serve as a carrier after being subjected to silicon coating treatment, template molecules are replaced by phenyl phosphonic acid, and surface imprinting and antigen determinant methods are used for synthesizing the molecular imprinting probe. The method comprises the following steps of preparing a cadmium telluride quantum dot solution; preparing quantum dot silicon-coated microspheres; preparing a composite material taking the quantum dot silicon-coated microspheres as a core and a molecular imprinted layer as a shell; and preparing the fluorescent molecular imprinting probe. The method has the advantages that high sensitivity of the quantum dots and high selectivity of molecular imprinting are combined by the fluorescent molecular imprinted polymer, the surface of the carrier is modified by the molecular imprinted layer, and recognition sites are close to the surface, so that target molecules can be easily and selectively recognized; the fluorescent probe synthesized by the antigen determinant method can be used for recognizing the target molecules tyrosine phosphorylated peptide, and fluorescence enhancement effects are achieved.

The invention discloses an in-situ self-assembled tetravalent platinum drug, a preparation method and application thereof. Cis-platinum is subjected to chemical reaction to generate cis-platinum oxide, and the cis-platinum oxide is further subjected to reaction with lysine residue to covalently modify tyrosine phosphorylated self-assembled short peptide to construct the tetravalent platinum drug.The tetravalent platinum drug can be self-assembled in situ to form supramolecular hydrogel with a nanofiber microstructure under the action of high-expression phosphatase on the surface of a tumor cell. Under the action of glutathione highly expressed in tumor cells, the platinum-containing nanofibers taken by the cells release a bivalent platinum drug to play a role in treatment. The formation of the hydrogel promotes the uptake of platinum drugs by tumor cells and increases the residence time of the platinum drugs in the tumor cells. Compared with traditional cis-platinum, the killing effect of the tetravalent platinum drug on tumor cells is not influenced by cell drug resistance, and the systematic toxicity is obviously reduced.

An adenoviral vector which expresses a dominant negative form of Stat3 called Stat3-EVA for the treatment of non-small cell lung carcinoma. This construct has two mutations in the DNA binding site of Stat3 which prevents binding to DNA but has no effect on tyrosine phosphorylation or dimerization.

The invention discloses 397 novel phosphorylation sites identified in carcinoma and / or leukemia, peptides (including AQUA peptides) comprising a phosphorylation site of the invention, antibodies specifically bind to a novel phosphorylation site of the invention, and diagnostic and therapeutic uses of the above.

An alternative HER-2 / neu product, herstatin, consists of subdomains I and II from the ectodomain of p185HER-2 and a unique 79 amino acid C-terminus encoded by intron 8. Recombinant herstatin added to cells was found to bind to and inhibit p185HER-2. The effects of ectopic expression of herstatin in combination with either p185HER-2 or with its homolog, the EGF receptor, in several cell lines was studied. Cotransfection of herstatin with HER-2 inhibited p185HER-2 levels and caused an approximate 8 fold reduction in p185 tyrosine phosphorylation. Inhibition of p185HER-2 tyrosine phosphorylation corresponded to a dramatic decline in colony formation by cells that coexpressed p185HER-2 and herstatin. Herstatin also interfered with EGF activation of the EGF receptor in cotransfected cells demonstrated by impaired receptor tyrosine phosphorylation, reduced receptor down-regulation, and growth suppression. For both p185HER-2 and the EGF receptor, the extent of inhibition was affected by the expression levels of herstatin relative to the receptor. Herstatin is an autoinhibitor of p185HER-2 and expands its inhibitory activity to another member of the group I family of receptor tyrosine kinases, the EGF receptor.

The invention relates to a method for quantitatively analyzing tyrosine-phosphorylated proteins. The method is characterized in that the dynamic change curve of the tyrosine phosphorylation level of asample to be tested is obtained based on an ELISA technology with a modified SH2 over parent as a first antibody, a standard curve is obtained with tyrosine-phosphorylated standard proteins as a reference sample in the detection process, and the quantitative analysis of the tyrosine phosphorylation level of the sample to be tested is realized with the standard curve as a reference. The method hasthe advantages of low cost, no sample pre-enrichment, good specificity and low detection limit. The ELISA technology is carried out in a well plate, and an apparatus is simple. The SH2 over parent adopted in the invention can be used to obtain a lot of proteins with a stable structure through bacterium expression and purification, so the experimental cost is greatly saved, the background is clear, and reconstruction is easy. The method has the same high affinity and high specificity to the tyrosine-phosphorylated proteins as antibody, has a broad spectrum, and can successfully realize the quantitative analysis of the tyrosine phosphorylation level of multiple complex samples.

It has been found out that among antibodies showing reactivity with wild type TGF-α, antibodies less reactive with G79A-substituted TGF-α have an excellent growth-suppressing effect on cancer cells having a mutated Ras gene. Further, it has been found out that most of these antibodies have an activity of inhibiting EGFR tyrosine phosphorylation and / or an induction-suppressing activity on vascular endothelial cells.

The present invention relates to a method for deep analysis of tyrosine phosphoproteomics based on competitive elution of affinity tyrosine phosphopeptide on a superbinder SH2. Specifically in the elution process of tyrosine phosphopeptide enrichment, a biotin-containing tyrosine phosphopeptide capable of strongly interacting with a superbinder SH2 is used as a competitive reagent to replace the traditional trifluoroacetic acid, the tyrosine phosphopeptide acting with the superbinder SH2 is sequentially eluted according to the intensity of the interaction, and the competitive reagent being notbound to the superbinder SH2 is bound by corresponding avidin so as not to affect the subsequent identification and analysis of the tyrosine phosphopeptide sample. According to the present invention,the method has advantages of rapidness, sensitivity, low cost and the like, can easily achieve the deep analysis of tyrosine phosphoproteomics, and can further provide the information of the interaction between the tyrosine phosphopeptide and the superbinder SH2.

The invention discloses a preparation method and application of naphthylamine compounds and salts thereof, concretely provides a method for synthesizing the naphthylamine compounds by taking 4-formylphenol as a substrate, and also provides a preparation method of hydrochloride and phosphate of the naphthylamine compounds. The preparation method has the characteristics of short synthesis route, cheap and easily available raw materials, simple post-treatment and purification, relatively high total yield and the like. The method has important significance for expanding the variety of naphthylamine derivatives and researching the naphthylamine derivatives in the aspects of biology and medicine. Meanwhile, the antitumor effect and mechanism of the prepared naphthylamine compounds and hydrochloride and phosphate thereof are further studied, and the result shows that the naphthylamine compounds and hydrochloride and phosphate thereof have the following advantages: (1) cancer cell proliferation, growth or migration is inhibited; and (2) cancer cell apoptosis is promoted or cancer cell migration capability or invasion capability is reduced, and meanwhile, the compounds can also be used as an inhibitor for tyrosine phosphorylation of STAT3.

The invention discloses 214 novel phosphorylation sites identified in signal transduction proteins and pathways underlying human carcinoma, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites / proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: Adaptor / Scaffold proteins, Cytoskeleton proteins, GTP Signaling proteins, Kinases, Metabolism proteins, Phosphatases / Phospho-diesterases / Proteases, Receptor proteins, RNA Processing proteins, Transcription proteins, Translation proteins, Transporter proteins, and Ubitquitin proteins, as well as other protein types.

The invention provides an effect of activating serine, threonine and tyrosine phosphorylation of an epidermal growth factor receptor (EGFR) by epigallocatechin gallate (EGCG), and the effect is similar to an epidermal growth factor (EGF), that is, the EGCG can serve as the EGF of a plant origin to be applied to promotion of epidermal repair and regeneration. The invention provides application of the EGCG to preparation of drugs and cosmetics for promoting epidermal repair and regeneration. The invention further provides the EGCG serving as the epidermal growth factor, an epidermal growth factor receptor activator and an epidermal growth factor receptor signal channel promoter.

The invention discloses 94 novel phosphorylation sites identified in carcinoma and leukemia, peptides (including AQUA peptides) comprising a phosphorylation site of the invention, antibodies that specifically bind to a novel phosphorylation site of the invention, and diagnostic and therapeutic uses of the above.

The invention discloses application of a beta-elimination and Michael nucleophilic addition method in study of phosphoproteomics, in particular a method for purifying tyrosine phosphopeptide. The method comprises the following steps of: eliminating phosphate modification groups on non-tyrosine phosphopeptide in protein hydrolysate by using beta-elimination and Michael nucleophilic addition; and enriching the tyrosine phosphopeptide which is not subjected to the elimination reaction by using a phosphoeptide enriching material. By utilizing the high specificity of the beta-elimination and Michael nucleophilic addition, the tyrosine phosphopeptide is purified from a complicated protein hydrolysate sample in high selectivity.

Among antibodies exhibiting reactivity to natural TGF[alpha], antibodies having low reactivity to G79A-substituted TGF[alpha] are identified as exhibiting superior antiproliferative activity against cancer cells having a mutation in the Ras gene. Further identified is that many of the antibodies also inhibit the tyrosine phosphorylation of EGFR and / or inhibit the induction of vascular endothelial cells.

The invention discloses 168 novel phosphorylation sites identified in signal transduction proteins and pathways downstream of, and including, EGFR kinase, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites / proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: Actin Binding proteins, Adaptor / Scaffold proteins, Calcium-Binding Proteins, Cell Cycle Regulation proteins, Cytoskeletal proteins, DNA Binding and Replication Proteins, GTPase Activating proteins, Guanine Nucleotide Exchange Factor proteins, Lipid Kinases, Receptor Tyrosine Kinases, Receptor Tyrosine Kinase ligands, Protein Kinases, Receptor and Protein Phosphatases, Transcription Factor proteins, Tumor Suppressor proteins, and Vesicle proteins.

The present invention is related to a novel protein p140 polypeptide which is a key protein involved in the signal transmission system of insulin; method for preparation of it; DNA encoding the said polypeptide; vector derived the said DNA; host cells transformed the said vector; antibody of the said polypeptide; pharmaceutical composition containing the said peptide or antibody; method for the prevention and / or treatment of diabetes, which is characterized by tyrosine phosphorylation of the said protein p140; agent for the prevention and / or treatment for the currently said the prevention and / or treatment method; agent for the prevention and / or treatment of diabetes, which is characterized by containing a compound which can tyrosine phosphorylation of protein p140, as active ingredient and the screening methods of the said prevention and / or treatment agent.Tyrosine phosphorylation of protein p140 is an essential step in the induction of hypoglycemia by glucose uptake. Method and agent of prevention and / or treatment based on tyrosine phosphorylation of protein p140 in the present invention is not only improve the diabetes-derived hyperglycemic conditions but are also useful for the treatment and / or prevention of diabetes, especially non-insulin dependent diabetes mellitus (NIDDM).

The present invention relates to a method of increasing cell proliferation in a population of pancreatic beta cells and a method of treating a subject for a condition associated with an insufficient level of insulin secretion. Also disclosed is a composition. The composition includes a dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1 A) inhibitor and a transforming growth factor beta (TGFP) superfamily signaling pathway inhibitor.

The invention discloses novel phosphorylation sites identified in signal transduction proteins and pathways, and provides phosphorylation-site specific antibodies and heavy-isotope labeled peptides (AQUA peptides) for the selective detection and quantification of these phosphorylated sites / proteins, as well as methods of using the reagents for such purpose. Among the phosphorylation sites identified are sites occurring in the following protein types: adaptor / scaffold proteins, adhesion / extracellular matrix protein, apoptosis proteins, calcium binding proteins, cell cycle regulation proteins, chaperone proteins, chromatin, DNA binding / repair / replication proteins, cytoskeletal proteins, endoplasmic reticulum or golgi proteins, enzyme proteins, G / regulator proteins, inhibitor proteins, motor / contractile proteins, phosphatase, protease, Ser / Thr protein kinases, Protein kinase (Tyr)s, receptor / channel / cell surface proteins, RNA binding proteins, transcriptional regulators, tumor suppressor proteins, ubiquitan conjugating system proteins and proteins of unknown function.