A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
An enzyme group that specifically dephosphorylates phosphotyrosyl residues in selected proteins. Together with PROTEIN-TYROSINE KINASE, it regulates tyrosine phosphorylation and dephosphorylation in cellular signal transduction and may play a role in cell growth control and carcinogenesis.
An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
An amino acid that occurs in endogenous proteins. Tyrosine phosphorylation and dephosphorylation plays a role in cellular signal transduction and possibly in cell growth control and carcinogenesis.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
A subtype of non-receptor protein tyrosine phosphatases that contain two SRC HOMOLOGY DOMAINS. Mutations in the gene for protein tyrosine phosphatase, non-receptor type 11 are associated with NOONAN SYNDROME.
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
A Src-homology domain-containing protein tyrosine phosphatase found in the CYTOSOL of hematopoietic cells. It plays a role in signal transduction by dephosphorylating signaling proteins that are activated or inactivated by PROTEIN-TYROSINE KINASES.
A subtype of non-receptor protein tyrosine phosphatases that includes two distinctive targeting motifs; an N-terminal motif specific for the INSULIN RECEPTOR, and a C-terminal motif specific for the SH3 domain containing proteins. This subtype includes a hydrophobic domain which localizes it to the ENDOPLASMIC RETICULUM.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
This enzyme is a lymphoid-specific src family tyrosine kinase that is critical for T-cell development and activation. Lck is associated with the cytoplasmic domains of CD4, CD8 and the beta-chain of the IL-2 receptor, and is thought to be involved in the earliest steps of TCR-mediated T-cell activation.
Established cell cultures that have the potential to propagate indefinitely.
An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.
Oxyvanadium ions in various states of oxidation. They act primarily as ion transport inhibitors due to their inhibition of Na(+)-, K(+)-, and Ca(+)-ATPase transport systems. They also have insulin-like action, positive inotropic action on cardiac ventricular muscle, and other metabolic effects.
Regions of AMINO ACID SEQUENCE similarity in the SRC-FAMILY TYROSINE KINASES that fold into specific functional tertiary structures. The SH1 domain is a CATALYTIC DOMAIN. SH2 and SH3 domains are protein interaction domains. SH2 usually binds PHOSPHOTYROSINE-containing proteins and SH3 interacts with CYTOSKELETAL PROTEINS.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF-related peptides including TRANSFORMING GROWTH FACTOR ALPHA; AMPHIREGULIN; and HEPARIN-BINDING EGF-LIKE GROWTH FACTOR. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.
Membrane-associated tyrosine-specific kinases encoded by the c-src genes. They have an important role in cellular growth control. Truncation of carboxy-terminal residues in pp60(c-src) leads to PP60(V-SRC) which has the ability to transform cells. This kinase pp60 c-src should not be confused with csk, also known as c-src kinase.
Src-family kinases that associate with T-CELL ANTIGEN RECEPTOR and phosphorylate a wide variety of intracellular signaling molecules.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A pyridoxal-phosphate protein that catalyzes the conversion of L-tyrosine to tyramine and carbon dioxide. The bacterial enzyme also acts on 3-hydroxytyrosine and, more slowly, on 3-hydroxyphenylalanine. (From Enzyme Nomenclature, 1992) EC
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
Agents that inhibit PROTEIN KINASES.
An enzyme that catalyzes the cleavage of tyrosine to phenol, pyruvate, and ammonia. It is a pyridoxal phosphate protein. The enzyme also forms pyruvate from D-tyrosine, L-cysteine, S-methyl-L-cysteine, L-serine, and D-serine, although at a slower rate. EC
A family of synthetic protein tyrosine kinase inhibitors. They selectively inhibit receptor autophosphorylation and are used to study receptor function.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
Non-receptor tyrosine kinases encoded by the C-ABL GENES. They are distributed in both the cytoplasm and the nucleus. c-Abl plays a role in normal HEMATOPOIESIS especially of the myeloid lineage. Oncogenic transformation of c-abl arises when specific N-terminal amino acids are deleted, releasing the kinase from negative regulation.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A subcategory of protein tyrosine phosphatases that contain SH2 type SRC HOMOLOGY DOMAINS. Many of the proteins in this class are recruited to specific cellular targets such as a cell surface receptor complexes via their SH2 domain.
A family of non-receptor, PROLINE-rich protein-tyrosine kinases.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymes
A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (CYTOSINE; THYMINE; and URACIL) and form the basic structure of the barbiturates.
A subclass of receptor-like protein tryosine phosphatases that contain a single cytosolic protein tyrosine phosphate domain and multiple extracellular fibronectin III-like domains.
Paxillin is a signal transducing adaptor protein that localizes to FOCAL ADHESIONS via its four LIM domains. It undergoes PHOSPHORYLATION in response to integrin-mediated CELL ADHESION, and interacts with a variety of proteins including VINCULIN; FOCAL ADHESION KINASE; PROTO-ONCOGENE PROTEIN PP60(C-SRC); and PROTO-ONCOGENE PROTEIN C-CRK.
A non-receptor protein tyrosine kinase that is localized to FOCAL ADHESIONS and is a central component of integrin-mediated SIGNAL TRANSDUCTION PATHWAYS. Focal adhesion kinase 1 interacts with PAXILLIN and undergoes PHOSPHORYLATION in response to adhesion of cell surface integrins to the EXTRACELLULAR MATRIX. Phosphorylated p125FAK protein binds to a variety of SH2 DOMAIN and SH3 DOMAIN containing proteins and helps regulate CELL ADHESION and CELL MIGRATION.
The rate dynamics in chemical or physical systems.
A subtype of non-receptor protein tyrosine phosphatase that is closely-related to PROTEIN TYROSINE PHOSPHATASE, NON-RECEPTOR TYPE 1. Alternative splicing of the mRNA for this phosphatase results in the production at two gene products, one of which includes a C-terminal nuclear localization domain that may be involved in the transport of the protein to the CELL NUCLEUS. Although initially referred to as T-cell protein tyrosine phosphatase the expression of this subtype occurs widely.
A phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
A non-receptor protein-tyrosine kinase that is expressed primarily in the BRAIN; OSTEOBLASTS; and LYMPHOID CELLS. In the CENTRAL NERVOUS SYSTEM focal adhesion kinase 2 modulates ION CHANNEL function and MITOGEN-ACTIVATED PROTEIN KINASES activity.
A subclass of receptor-like protein tryosine phosphatases that contain short highly glycosylated extracellular domains and two active cytosolic protein tyrosine phosphatase domains.
A receptor tyrosine kinase that is involved in HEMATOPOIESIS. It is closely related to FMS PROTO-ONCOGENE PROTEIN and is commonly mutated in acute MYELOID LEUKEMIA.
An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.
LACTAMS forming compounds with a ring size of approximately 1-3 dozen atoms.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
A signal transducing adaptor protein that links extracellular signals to the MAP KINASE SIGNALING SYSTEM. Grb2 associates with activated EPIDERMAL GROWTH FACTOR RECEPTOR and PLATELET-DERIVED GROWTH FACTOR RECEPTORS via its SH2 DOMAIN. It also binds to and translocates the SON OF SEVENLESS PROTEINS through its SH3 DOMAINS to activate PROTO-ONCOGENE PROTEIN P21(RAS).
Hydrocarbon rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
Benzene rings which contain two ketone moieties in any position. They can be substituted in any position except at the ketone groups.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A subcategory of protein tyrosine phosphatases that occur in the CYTOPLASM. Many of the proteins in this category play a role in intracellular signal transduction.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Proteins prepared by recombinant DNA technology.
A Janus kinase subtype that is involved in signaling from GROWTH HORMONE RECEPTORS; PROLACTIN RECEPTORS; and a variety of CYTOKINE RECEPTORS such as ERYTHROPOIETIN RECEPTORS and INTERLEUKIN RECEPTORS. Dysregulation of Janus kinase 2 due to GENETIC TRANSLOCATIONS have been associated with a variety of MYELOPROLIFERATIVE DISORDERS.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
A cell surface receptor for INSULIN. It comprises a tetramer of two alpha and two beta subunits which are derived from cleavage of a single precursor protein. The receptor contains an intrinsic TYROSINE KINASE domain that is located within the beta subunit. Activation of the receptor by INSULIN results in numerous metabolic changes including increased uptake of GLUCOSE into the liver, muscle, and ADIPOSE TISSUE.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC, it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of a N-terminal catalytic domain and a large C-terminal domain that is enriched in PROLINE, GLUTAMIC ACID, SERINE, and THREONINE residues (PEST sequences). The phosphatase subtype is ubiquitously expressed and implicated in the regulation of a variety of biological processes such as CELL MOVEMENT; CYTOKINESIS; focal adhesion disassembly; and LYMPHOCYTE ACTIVATION.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
A 6-kDa polypeptide growth factor initially discovered in mouse submaxillary glands. Human epidermal growth factor was originally isolated from urine based on its ability to inhibit gastric secretion and called urogastrone. Epidermal growth factor exerts a wide variety of biological effects including the promotion of proliferation and differentiation of mesenchymal and EPITHELIAL CELLS. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form.
3-Phenylchromones. Isomeric form of FLAVONOIDS in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
A subclass of receptor-like protein tryosine phosphatases that contain an extracellular fibronectin III-like domain along with a carbonic anhydrase-like domain.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
A family of signaling adaptor proteins that contain SRC HOMOLOGY DOMAINS. Many members of this family are involved in transmitting signals from CELL SURFACE RECEPTORS to MITOGEN-ACTIVATED PROTEIN KINASES.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
Corrosive oxidant, explosive; additive to diesel and rocket fuels; causes skin and lung irritation; proposed war gas. A useful reagent for studying the modification of specific amino acids, particularly tyrosine residues in proteins. Has also been used for studying carbanion formation and for detecting the presence of double bonds in organic compounds.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
Cell surface protein-tyrosine kinase receptors for HEPATOCYTE GROWTH FACTOR. They consist of an extracellular alpha chain which is disulfide-linked to the transmembrane beta chain. The cytoplasmic portion contains the catalytic domain and sites critical for the regulation of kinase activity. Mutations of the gene for PROTO-ONCOGENE PROTEINS C-MET are associated with papillary renal carcinoma and other neoplasia.
Physiologically inactive substances that can be converted to active enzymes.
A cell line derived from cultured tumor cells.
Specific receptors on cell membranes that react with PLATELET-DERIVED GROWTH FACTOR, its analogs, or antagonists. The alpha PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA) and the beta PDGF receptor (RECEPTOR, PLATELET-DERIVED GROWTH FACTOR BETA) are the two principle types of PDGF receptors. Activation of the protein-tyrosine kinase activity of the receptors occurs by ligand-induced dimerization or heterodimerization of PDGF receptor types.
Major constituent of the cytoskeleton found in the cytoplasm of eukaryotic cells. They form a flexible framework for the cell, provide attachment points for organelles and formed bodies, and make communication between parts of the cell possible.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
A protein-tyrosine kinase receptor that is specific for STEM CELL FACTOR. This interaction is crucial for the development of hematopoietic, gonadal, and pigment stem cells. Genetic mutations that disrupt the expression of PROTO-ONCOGENE PROTEINS C-KIT are associated with PIEBALDISM, while overexpression or constitutive activation of the c-kit protein-tyrosine kinase is associated with tumorigenesis.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
Adherence of cells to surfaces or to other cells.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
Surface ligands, usually glycoproteins, that mediate cell-to-cell adhesion. Their functions include the assembly and interconnection of various vertebrate systems, as well as maintenance of tissue integration, wound healing, morphogenic movements, cellular migrations, and metastasis.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
Crk-associated substrate was originally identified as a highly phosphorylated 130 kDa protein that associates with ONCOGENE PROTEIN CRK and ONCOGENE PROTEIN SRC. It is a signal transducing adaptor protein that undergoes tyrosine PHOSPHORYLATION in signaling pathways that regulate CELL MIGRATION and CELL PROLIFERATION.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A family of cell surface receptors that were originally identified by their structural homology to neurotropic TYROSINE KINASES and referred to as orphan receptors because the associated ligand and signaling pathways were unknown. Evidence for the functionality of these proteins has been established by experiments showing that disruption of the orphan receptor genes results in developmental defects.
Retrovirus-associated DNA sequences (src) originally isolated from the Rous sarcoma virus (RSV). The proto-oncogene src (c-src) codes for a protein that is a member of the tyrosine kinase family and was the first proto-oncogene identified in the human genome. The human c-src gene is located at 20q12-13 on the long arm of chromosome 20.
Translation products of a fusion gene derived from CHROMOSOMAL TRANSLOCATION of C-ABL GENES to the genetic locus of the breakpoint cluster region gene on chromosome 22. Several different variants of the bcr-abl fusion proteins occur depending upon the precise location of the chromosomal breakpoint. These variants can be associated with distinct subtypes of leukemias such as PRECURSOR CELL LYMPHOBLASTIC LEUKEMIA-LYMPHOMA; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE; and NEUTROPHILIC LEUKEMIA, CHRONIC.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.
A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
The movement of cells from one location to another. Distinguish from CYTOKINESIS which is the process of dividing the CYTOPLASM of a cell.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.
A CELL LINE derived from human T-CELL LEUKEMIA and used to determine the mechanism of differential susceptibility to anti-cancer drugs and radiation.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
A structurally-related group of signaling proteins that are phosphorylated by the INSULIN RECEPTOR PROTEIN-TYROSINE KINASE. The proteins share in common an N-terminal PHOSPHOLIPID-binding domain, a phosphotyrosine-binding domain that interacts with the phosphorylated INSULIN RECEPTOR, and a C-terminal TYROSINE-rich domain. Upon tyrosine phosphorylation insulin receptor substrate proteins interact with specific SH2 DOMAIN-containing proteins that are involved in insulin receptor signaling.
Substances that inhibit or prevent the proliferation of NEOPLASMS.
A signal transducer and activator of transcription that mediates cellular responses to a variety of CYTOKINES. Stat5 activation is associated with transcription of CELL CYCLE regulators such as CYCLIN KINASE INHIBITOR P21 and anti-apoptotic genes such as BCL-2 GENES. Stat5 is constitutively activated in many patients with acute MYELOID LEUKEMIA.
A protein-tyrosine kinase receptor that is specific for NERVE GROWTH FACTOR; NEUROTROPHIN 3; neurotrophin 4, neurotrophin 5. It plays a crucial role in pain sensation and thermoregulation in humans. Gene mutations that cause loss of receptor function are associated with CONGENITAL INSENSITIVITY TO PAIN WITH ANHIDROSIS, while gene rearrangements that activate the protein-tyrosine kinase function are associated with tumorigenesis.
A Janus kinase subtype that is involved in signaling from a broad variety of CYTOKINE RECEPTORS. The TYK2 kinase is considered the founding member of the janus kinase family and was initially discovered as a signaling partner for the INTERFERON ALPHA-BETA RECEPTOR. The kinase has since been shown to signal from several INTERLEUKIN RECEPTORS.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
Signal transducing adaptor proteins that contain SRC HOMOLOGY DOMAINS and play a role in CYTOSKELETON reorganization. c-crk protein is closely related to ONCOGENE PROTEIN V-CRK and includes several alternatively spliced isoforms.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
The relationship between the dose of an administered drug and the response of the organism to the drug.
Elements of limited time intervals, contributing to particular results or situations.
A class of proteins involved in the transport of molecules via TRANSPORT VESICLES. They perform functions such as binding to the cell membrane, capturing cargo molecules and promoting the assembly of CLATHRIN. The majority of adaptor proteins exist as multi-subunit complexes, however monomeric varieties have also been found.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment.
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
A subtype of non-receptor protein tyrosine phosphatases that is characterized by the presence of an amino-terminal FERM domain, an intervening region containing five different PDZ domains, and a carboxyl-terminal phosphatase domain. In addition to playing a role as a regulator of the FAS RECEPTOR activity this subtype interacts via its PDZ and FERM domains with a variety of INTRACELLULAR SIGNALING PROTEINS and CYTOSKELETAL PROTEINS.
Transforming proteins encoded by the abl oncogenes. Oncogenic transformation of c-abl to v-abl occurs by insertional activation that results in deletions of specific N-terminal amino acids.
A PDGF receptor that binds specifically to the PDGF-B chain. It contains a protein-tyrosine kinase activity that is involved in SIGNAL TRANSDUCTION.
Mitogenic peptide growth hormone carried in the alpha-granules of platelets. It is released when platelets adhere to traumatized tissues. Connective tissue cells near the traumatized region respond by initiating the process of replication.
The sum of the weight of all the atoms in a molecule.
Molecules on the surface of T-lymphocytes that recognize and combine with antigens. The receptors are non-covalently associated with a complex of several polypeptides collectively called CD3 antigens (ANTIGENS, CD3). Recognition of foreign antigen and the major histocompatibility complex is accomplished by a single heterodimeric antigen-receptor structure, composed of either alpha-beta (RECEPTORS, ANTIGEN, T-CELL, ALPHA-BETA) or gamma-delta (RECEPTORS, ANTIGEN, T-CELL, GAMMA-DELTA) chains.
Cell changes manifested by escape from control mechanisms, increased growth potential, alterations in the cell surface, karyotypic abnormalities, morphological and biochemical deviations from the norm, and other attributes conferring the ability to invade, metastasize, and kill.
The major protein constituents of milk are CASEINS and whey proteins such as LACTALBUMIN and LACTOGLOBULINS. IMMUNOGLOBULINS occur in high concentrations in COLOSTRUM and in relatively lower concentrations in milk. (Singleton and Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed, p554)
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Lymphocytes responsible for cell-mediated immunity. Two types have been identified - cytotoxic (T-LYMPHOCYTES, CYTOTOXIC) and helper T-lymphocytes (T-LYMPHOCYTES, HELPER-INDUCER). They are formed when lymphocytes circulate through the THYMUS GLAND and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen.
The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.
A Janus kinase subtype that is predominantly expressed in hematopoietic cell. It is involved in signaling from a broad variety of CYTOKINE RECEPTORS including ones that utilize the INTERLEUKIN RECEPTOR COMMON GAMMA SUBUNIT.
Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.
Proto-oncogene proteins that are guanine nucleotide exchange factors for RHO GTPASES. They also function as signal transducing adaptor proteins.
Chemically stimulated aggregation of cell surface receptors, which potentiates the action of the effector cell.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
Members of the src-family tyrosine kinase family that are strongly expressed in MYELOID CELLS and B-LYMPHOCYTES.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Receptor protein-tyrosine kinases involved in the signaling of GLIAL CELL-LINE DERIVED NEUROTROPHIC FACTOR ligands. They contain an extracellular cadherin domain and form a receptor complexes with GDNF RECEPTORS. Mutations in ret protein are responsible for HIRSCHSPRUNG DISEASE and MULTIPLE ENDOCRINE NEOPLASIA TYPE 2.
Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
A CELL LINE derived from a PHEOCHROMOCYTOMA of the rat ADRENAL MEDULLA. PC12 cells stop dividing and undergo terminal differentiation when treated with NERVE GROWTH FACTOR, making the line a useful model system for NERVE CELL differentiation.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990)
A signal transducer and activator of transcription that mediates cellular responses to INTERFERONS. Stat1 interacts with P53 TUMOR SUPPRESSOR PROTEIN and regulates expression of GENES involved in growth control and APOPTOSIS.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
A microfilament protein that interacts with F-ACTIN and regulates cortical actin assembly and organization. It is also an SH3 DOMAIN containing phosphoprotein, and it mediates tyrosine PHOSPHORYLATION based SIGNAL TRANSDUCTION by PROTO-ONCOGENE PROTEIN PP60(C-SRC).
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.
A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.
An eph family receptor found widely expressed in embryonic and adult tissues. High levels of EphB2 receptor are observed in growing AXONS and NERVE FIBERS. Several isoforms of the protein exist due to multiple alternative mRNA splicing.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
Eukaryotic cell line obtained in a quiescent or stationary phase which undergoes conversion to a state of unregulated growth in culture, resembling an in vitro tumor. It occurs spontaneously or through interaction with viruses, oncogenes, radiation, or drugs/chemicals.
The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
Proteins coded by oncogenes. They include proteins resulting from the fusion of an oncogene and another gene (ONCOGENE PROTEINS, FUSION).
A beta-hydroxylated derivative of phenylalanine. The D-form of dihydroxyphenylalanine has less physiologic activity than the L-form and is commonly used experimentally to determine whether the pharmacological effects of LEVODOPA are stereospecific.
Cell surface receptors that bind growth or trophic factors with high affinity, triggering intracellular responses which influence the growth, differentiation, or survival of cells.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
Clonal hematopoetic disorder caused by an acquired genetic defect in PLURIPOTENT STEM CELLS. It starts in MYELOID CELLS of the bone marrow, invades the blood and then other organs. The condition progresses from a stable, more indolent, chronic phase (LEUKEMIA, MYELOID, CHRONIC PHASE) lasting up to 7 years, to an advanced phase composed of an accelerated phase (LEUKEMIA, MYELOID, ACCELERATED PHASE) and BLAST CRISIS.
Differentiation antigens residing on mammalian leukocytes. CD stands for cluster of differentiation, which refers to groups of monoclonal antibodies that show similar reactivity with certain subpopulations of antigens of a particular lineage or differentiation stage. The subpopulations of antigens are also known by the same CD designation.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
The structural and functional changes by which SPERMATOZOA become capable of oocyte FERTILIZATION. It normally requires exposing the sperm to the female genital tract for a period of time to bring about increased SPERM MOTILITY and the ACROSOME REACTION before fertilization in the FALLOPIAN TUBES can take place.
Transport proteins that carry specific substances in the blood or across cell membranes.
A subclass of receptor-like protein tryosine phosphatases that contain a short extracellular domain, a cytosolic kinase-interaction domain, and single protein tyrosine kinase domain.
The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
Factors which enhance the growth potentialities of sensory and sympathetic nerve cells.
Antibodies produced by a single clone of cells.
One of the catecholamine NEUROTRANSMITTERS in the brain. It is derived from TYROSINE and is the precursor to NOREPINEPHRINE and EPINEPHRINE. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of receptors (RECEPTORS, DOPAMINE) mediate its action.
Multifunctional growth factor which regulates both cell growth and cell motility. It exerts a strong mitogenic effect on hepatocytes and primary epithelial cells. Its receptor is PROTO-ONCOGENE PROTEINS C-MET.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
High-molecular weight glycoproteins uniquely expressed on the surface of LEUKOCYTES and their hemopoietic progenitors. They contain a cytoplasmic protein tyrosine phosphatase activity which plays a role in intracellular signaling from the CELL SURFACE RECEPTORS. The CD45 antigens occur as multiple isoforms that result from alternative mRNA splicing and differential usage of three exons.
A protein-tyrosine kinase receptor that is specific for BRAIN-DERIVED NEUROTROPHIC FACTOR; NEUROTROPHIN 3; neurotrophin 4 and neurotrophin 5. It is widely expressed in nervous tissue and plays a role in mediating the effects of neurotrophins on growth and differentiation of neuronal cells.
A group of 1,2-benzenediols that contain the general formula R-C6H5O2.
Azoles of one NITROGEN and two double bonds that have aromatic chemical properties.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.

The hematopoietic-specific adaptor protein gads functions in T-cell signaling via interactions with the SLP-76 and LAT adaptors. (1/13395)

BACKGROUND: The adaptor protein Gads is a Grb2-related protein originally identified on the basis of its interaction with the tyrosine-phosphorylated form of the docking protein Shc. Gads protein expression is restricted to hematopoietic tissues and cell lines. Gads contains a Src homology 2 (SH2) domain, which has previously been shown to have a similar binding specificity to that of Grb2. Gads also possesses two SH3 domains, but these have a distinct binding specificity to those of Grb2, as Gads does not bind to known Grb2 SH3 domain targets. Here, we investigated whether Gads is involved in T-cell signaling. RESULTS: We found that Gads is highly expressed in T cells and that the SLP-76 adaptor protein is a major Gads-associated protein in vivo. The constitutive interaction between Gads and SLP-76 was mediated by the carboxy-terminal SH3 domain of Gads and a 20 amino-acid proline-rich region in SLP-76. Gads also coimmunoprecipitated the tyrosine-phosphorylated form of the linker for activated T cells (LAT) adaptor protein following cross-linking of the T-cell receptor; this interaction was mediated by the Gads SH2 domain. Overexpression of Gads and SLP-76 resulted in a synergistic augmentation of T-cell signaling, as measured by activation of nuclear factor of activated T cells (NFAT), and this cooperation required a functional Gads SH2 domain. CONCLUSIONS: These results demonstrate that Gads plays an important role in T-cell signaling via its association with SLP-76 and LAT. Gads may promote cross-talk between the LAT and SLP-76 signaling complexes, thereby coupling membrane-proximal events to downstream signaling pathways.  (+info)

Tyrosine phosphorylation is required for actin-based motility of vaccinia but not Listeria or Shigella. (2/13395)

Studies of the actin-based motility of pathogens have provided important insights into the events occurring at the leading edge of motile cells [1] [2] [3]. To date, several actin-cytoskeleton-associated proteins have been implicated in the motility of Listeria or Shigella: vasodilator-stimulated phosphoprotein (VASP), vinculin and the actin-related protein complex of Arp2 and Arp3 [4] [5] [6] [7]. To further investigate the underlying mechanism of actin-tail assembly, we examined the localization of components of the actin cytoskeleton including Arp3, VASP, vinculin and zyxin during vaccinia, Listeria and Shigella infections. The most striking difference between the systems was that a phosphotyrosine signal was observed only at the site of vaccinia actin-tail assembly. Micro-injection experiments demonstrated that a phosphotyrosine protein plays an important role in vaccinia actin-tail formation. In addition, we observed a phosphotyrosine signal on clathrin-coated vesicles that have associated actin-tail-like structures and on endogenous vesicles in Xenopus egg extracts which are able to nucleate actin tails [8] [9]. Our observations indicate that a host phosphotyrosine protein is required for the nucleation of actin filaments by vaccinia and suggest that this phosphoprotein might be associated with cellular membranes that can nucleate actin.  (+info)

Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation. (3/13395)

Cbl-b, a mammalian homolog of Cbl, consists of an N-terminal region (Cbl-b-N) highly homologous to oncogenic v-Cbl, a Ring finger, and a C-terminal region containing multiple proline-rich stretches and potential tyrosine phosphorylation sites. In the present study, we demonstrate that upon engagement of the T cell receptor (TCR), endogenous Cbl-b becomes rapidly tyrosine-phosphorylated. In heterogeneous COS-1 cells, Cbl-b was phosphorylated on tyrosine residues by both Syk- (Syk/Zap-70) and Src- (Fyn/Lck) family kinases, with Syk kinase inducing the most prominent effect. Syk associates and phosphorylates Cbl-b in Jurkat T cells. A Tyr-316 Cbl-binding site in Syk was required for the association with and for the maximal tyrosine phosphorylation of Cbl-b. Mutation at a loss-of-function site (Gly-298) in Cbl-b-N disrupts its interaction with Syk. Cbl-b constitutively binds Grb2 and becomes associated with Crk-L upon TCR stimulation. The Grb2- and the Crk-L-binding regions were mapped to the C-terminus of Cbl-b. The Crk-L-binding sites were further determined to be Y655DVP and Y709KIP, with the latter being the primary binding site. Taken together, these results implicate that Cbl-b is involved in TCR-mediated intracellular signaling pathways.  (+info)

Identification of a novel family of targets of PYK2 related to Drosophila retinal degeneration B (rdgB) protein. (4/13395)

The protein tyrosine kinase PYK2 has been implicated in signaling pathways activated by G-protein-coupled receptors, intracellular calcium, and stress signals. Here we describe the molecular cloning and characterization of a novel family of PYK2-binding proteins designated Nirs (PYK2 N-terminal domain-interacting receptors). The three Nir proteins (Nir1, Nir2, and Nir3) bind to the amino-terminal domain of PYK2 via a conserved sequence motif located in the carboxy terminus. The primary structures of Nirs reveal six putative transmembrane domains, a region homologous to phosphatidylinositol (PI) transfer protein, and an acidic domain. The Nir proteins are the human homologues of the Drosophila retinal degeneration B protein (rdgB), a protein implicated in the visual transduction pathway in flies. We demonstrate that Nirs are calcium-binding proteins that exhibit PI transfer activity in vivo. Activation of PYK2 by agents that elevate intracellular calcium or by phorbol ester induce tyrosine phosphorylation of Nirs. Moreover, PYK2 and Nirs exhibit similar expression patterns in several regions of the brain and retina. In addition, PYK2-Nir complexes are detected in lysates prepared from cultured cells or from brain tissues. Finally, the Nir1-encoding gene is located at human chromosome 17p13.1, in proximity to a locus responsible for several human retinal diseases. We propose that the Nir and rdgB proteins represent a new family of evolutionarily conserved PYK2-binding proteins that play a role in the control of calcium and phosphoinositide metabolism downstream of G-protein-coupled receptors.  (+info)

Identification of a new Pyk2 target protein with Arf-GAP activity. (5/13395)

Protein tyrosine kinase Pyk2 is activated by a variety of G-protein-coupled receptors and by extracellular signals that elevate intracellular Ca2+ concentration. We have identified a new Pyk2 binding protein designated Pap. Pap is a multidomain protein composed of an N-terminal alpha-helical region with a coiled-coil motif, followed by a pleckstrin homology domain, an Arf-GAP domain, an ankyrin homology region, a proline-rich region, and a C-terminal SH3 domain. We demonstrate that Pap forms a stable complex with Pyk2 and that activation of Pyk2 leads to tyrosine phosphorylation of Pap in living cells. Immunofluorescence experiments demonstrate that Pap is localized in the Golgi apparatus and at the plasma membrane, where it is colocalized with Pyk2. In addition, in vitro recombinant Pap exhibits strong GTPase-activating protein (GAP) activity towards the small GTPases Arf1 and Arf5 and weak activity towards Arf6. Addition of recombinant Pap protein to Golgi preparations prevented Arf-dependent generation of post-Golgi vesicles in vitro. Moreover, overexpression of Pap in cultured cells reduced the constitutive secretion of a marker protein. We propose that Pap functions as a GAP for Arf and that Pyk2 may be involved in regulation of vesicular transport through its interaction with Pap.  (+info)

BLNK required for coupling Syk to PLC gamma 2 and Rac1-JNK in B cells. (6/13395)

Signaling through the B cell receptor (BCR) is essential for B cell function and development. Despite the key role of Syk in BCR signaling, little is known about the mechanism by which Syk transmits downstream effectors. BLNK (B cell LiNKer protein), a substrate for Syk, is now shown to be essential in activating phospholipase C (PLC)gamma 2 and JNK. The BCR-induced PLC gamma 2 activation, but not the JNK activation, was restored by introduction of PLC gamma 2 membrane-associated form into BLNK-deficient B cells. As JNK activation requires both Rac1 and PLC gamma 2, our results suggest that BLNK regulates the Rac1-JNK pathway, in addition to modulating PLC gamma 2 localization.  (+info)

Role of nitric oxide in lipopolysaccharide-induced hepatic injury in D-galactosamine-sensitized mice as an experimental endotoxic shock model. (7/13395)

The role of nitric oxide (NO) in lipopolysaccharide (LPS)-induced hepatic injury was studied in D-galactosamine (D-GalN)-sensitized mice. The inducible isoform of NO synthase (iNOS) was immunohistochemically detected on hepatocytes around blood vessels in livers of mice injected with D-GalN and LPS not on hepatocytes in mice injected with D-GalN or LPS alone, although mRNA for iNOS was found in those mice. Nitrotyrosine (NT) was also found in livers of mice injected with D-GalN and LPS. The localization of NT was consistent with that of iNOS, and the time courses of NT and iNOS expression were almost the same. Expression of iNOS and NT was detected exclusively in the hepatic lesions of mice injected with D-GalN and LPS. Anti-tumor necrosis factor alpha neutralizing antibody inhibited iNOS and NT expression and hepatic injury. The results suggested that NO from iNOS may play a role in LPS-induced hepatic injury on D-GalN-sensitized mice as an experimental endotoxic shock model.  (+info)

Yops of Yersinia enterocolitica inhibit receptor-dependent superoxide anion production by human granulocytes. (8/13395)

The virulence plasmid-borne genes encoding Yersinia adhesin A (YadA) and several Yersinia secreted proteins (Yops) are involved in the inhibition of phagocytosis and killing of Yersinia enterocolitica by human granulocytes. One of these Yops, YopH, dephosphorylates multiple tyrosine-phosphorylated proteins in eukaryotic cells and is involved in the inhibition of phagocytosis of Y. enterocolitica by human granulocytes. We investigated whether antibody- and complement-opsonized plasmid-bearing (pYV+) Y. enterocolitica inhibits O2- production by human granulocytes in response to various stimuli and whether YopH is involved. Granulocytes were preincubated with mutant strains unable to express YadA or to secrete Yops or YopH. O2- production by granulocytes during stimulation was assessed by measuring the reduction of ferricytochrome c. PYV+ Y. enterocolitica inhibited O2- production by granulocytes incubated with opsonized Y. enterocolitica or N-formyl-Met-Leu-Phe (f-MLP). This inhibitory effect mediated by pYV did not affect receptor-independent O2- production by granulocytes in response to phorbol myristate acetate, indicating that NADPH activity remained unaffected after activation of protein kinase C. The inhibition of f-MLP-induced O2- production by granulocytes depends on the secretion of Yops and not on the expression of YadA. Insertional inactivation of the yopH gene abrogated the inhibition of phagocytosis of antibody- and complement-opsonized Y. enterocolitica by human granulocytes but not of the f-MLP-induced O2- production by granulocytes or tyrosine phosphorylation of granulocyte proteins. These findings suggest that the specific targets for YopH are not present in f-MLP receptor-linked signal transduction and that other Yop-mediated mechanisms are involved.  (+info)

The protein kinase activity associated with pp60src, the transforming protein of RSV, phosphorylates tyrosine when assayed in an immunoprecipitate. This observation is surprising because protein modification by way of phosphorylation of tyrosine is unprecedented (28, 29). It is nonetheless real. We have found that chicken cells (Table 1) and mouse, rat, and hamster cells (data not shown) all contain readily detectable amounts of Tyr(P). This modified amino acid appears to have escaped detection before because it is rare (phosphoserine and phosphothreonine together being about 3000 times more abundant) and because it and phosphothreonine are difficult to separate by traditional electrophoretic procedures. Because there is a 7-fold increase in the abundance of Tyr(P) in proteins in cells transformed by RSV and because pp60src itself contains Tyr(P), it seems likely that pp60src phosphorylates tyrosine in vivo as well as in vitro. We suggest that pp60src is a protein kinase and that the ...
The single tyrosine residue in both pig and cow intestinal Ca2+-binding proteins fluoresces at 303 nm although the crystal structure of the cow protein shows a hydrogen bond between the hydroxy group of the tyrosine and glutamate-38 [Szebenyi & Moffat (1986) J. Biol. Chem. 261, 8761-8777]. The latter interaction suggests that tyrosinate fluorescence should dominate the emission spectra of these proteins. A fluorescence difference spectrum, produced by subtracting the spectrum of free tyrosine from the spectrum of the protein, gives a peak at 334 nm due to ionized tyrosine. That this component of the emission spectrum is not due to a tryptophan-containing contaminant is shown by its elimination when the protein is denatured by guanidine and when glutamate-38 is protonated. We conclude that, in solution, the tyrosine residue in this protein interacts occasionally with glutamate-38 but that a permanent hydrogen bond is not formed. ...
TY - JOUR. T1 - Insulin phosphorylates tyrosine residue 464 of tub and translocates tubby into the nucleus in hircb cells. AU - Kim, Jin Wook. AU - Kim, Hyeon Soo. AU - Kim, Sang Dae. AU - Park, Jung Yul. N1 - Funding Information: This study was supported by a Korea University Grant (K-1220321) and also supported by the Kil Chung Hee Fellowship Fund.. PY - 2014. Y1 - 2014. N2 - Background: The tubby protein has a motif that might be relevant for its action in the insulin signaling pathway. Previous studies have indicated that tubby undergoes phosphorylation on tyrosine residues in response to several stimuli and is known to localize in the nucleus as well as in the plasma membrane. However, the relationship between phosphorylation and nuclear translocation is not well understood. Here, we report that insulin directly phosphorylates tubby, which translocates into the nucleus. Methods: The effects of insulin on Tubby were performed with Western blot. The immunoprecipitation and confocal microscopy ...
TY - JOUR. T1 - A role for cholecystokinin-stimulated protein tyrosine phosphorylation in regulated secretion by the pancreatic acinar cell. AU - Lutz, M. P.. AU - Sutor, S. L.. AU - Abraham, R. T.. AU - Miller, L. J.. PY - 1993/1/1. Y1 - 1993/1/1. N2 - Cholecystokinin (CCK) is a gastrointestinal hormone that acts through a G protein-coupled receptor to stimulate pancreatic enzyme secretion. In this work, we demonstrate that CCK stimulation of dispersed pancreatic acini results in increased tyrosine phosphorylation of several cellular proteins. This is mediated via a calcium-dependent pathway, also activated by a phenethyl ester analogue of CCK and calcium ionophores, and by a protein kinase C-dependent cascade, also activated by the phorbol ester 12-O- tetradecanoylphorbol-13-acetate. All demonstrable stimulated tyrosine phosphorylation events were inhibited by genistein, with different subsets of proteins affected by staurosporine and H-7. The importance of tyrosine phosphorylation events in ...
1. Plasma amino acid kinetics were determined in hospitalized patients receiving one of three intravenous solutions: isotonic amino acids, isotonic sodium chloride, or total parenteral nutrition.. 2. Whole body amino acid appearance, oxidation and incorporation into protein were estimated with two different isotopically labelled amino acids: l-[1-14C]leucine and l-[U-14C]tyrosine.. 3. A positive correlation was obtained between whole body amino acid appearance, oxidation and incorporation into protein with the two isotopically labelled amino acids.. 4. Derivation of whole body protein kinetics with l-[U-14C]tyrosine consistently gave higher values than those obtained from l-[1-14C]leucine, presumably due in part to the contribution of phenylalanine hydroxylation to plasma tyrosine appearance. However, the percentages of amino acid appearance oxidized and used for protein synthesis were similar.. 5. It can be concluded that estimates of whole body protein kinetics are qualitatively similar when ...
Members of the Eph family of receptor tyrosine kinases exhibit a striking degree of amino acid homology, particularly notable in the kinase and membrane-proximal regions. A mutagenesis approach was taken to address the functions of specific conserved tyrosine residues within these catalytic and juxtamembrane domains. Ligand stimulation of wild-type EphB2 in neuronal NG108-15 cells resulted in an upregulation of catalytic activity and an increase in cellular tyrosine phosphorylation, accompanied by a retraction of neuritic processes. Tyrosine-to-phenylalanine substitutions within the conserved juxtamembrane motif abolished these responses. The mechanistic basis for these observations was examined using the highly related EphA4 receptor in a continuous coupled kinase assay. Tandem mass spectrometry experiments confirmed autophosphorylation of the two juxtamembrane tyrosine residues and also identified a tyrosine within the kinase domain activation segment as a phosphorylation site. Kinetic ...
TY - JOUR. T1 - Disease tropism of c-erbB. T2 - Effects of carboxyl-terminal tyrosine and internal mutations on tissue-specific transformation. AU - Pelley, R. J.. AU - Maihle, Nita Jane. AU - Boerkoel, C.. AU - Shu, H. K.. AU - Carter, T. H.. AU - Moscovici, C.. AU - Kung, H. J.. PY - 1989/1/1. Y1 - 1989/1/1. N2 - Avian leukosis virus induces erythroleukemia in chickens by proviral insertional mutation of the proto-oncogene c-erbB. The product of the insertionally activated c-erbB locus lacks the extracellular ligand-binding domain and is strictly leukemogenic. It has previously been demonstrated that the disease spectrum associated with aberrant c-erbB expression can be expanded by structural perturbation of the cytoplasmic domain of this protein. In this report, we use mutagenesis and retroviral vectors to identify specific mutations in the carboxyl-terminal domain of the insertionally activated c-erbB product that are sufficient to activate the sarcomagenic potential of this protein. ...
Cross-linking of FcγRIIIA (CD16) receptor on natural killer (NK) cells induces receptor-associated tyrosine kinase activation and tyrosine phosphorylation of numerous intracellular proteins, including phospholipase C (PLC)-γ1, PLC-γ2 and the associated ζ chain. Here we report that Vav, a proto-oncogene, also became tyrosine phosphorylated upon stimulation of CD16 in interleukin 2-activated NK cells (LAK-NK) as well as in an NK cell line, NK3.3. In addition, we observed that in LAK-NK cells, Vav was associated with a 70 kDa protein that also became tyrosine phosphorylated upon CD16 cross-linking. The association of this 70 kDa protein with Vav was disrupted by ionic detergent treatment. Tyrosine phosphorylation of Vav was inhibited by herbimycin A, a specific tyrosine kinase inhibitor. In vitro kinase assays with Vav immunoprecipitates derived from NK3.3 cells or LAK-NK cells resulted in the appearance of a phosphorylated 58 kDa protein, suggesting the presence of a kinase within the Vav ...
Intercellular adhesion molecules (ICAM)-1 and -3 coexist on T lymphocytes and are counter-receptors for the integrin LFA-1. Signaling through ICAM-3 stimulates a number of T cell functions and involves phosphorylation of Fyn, Lck, CD45, and other proteins. In contrast, this type of specific signaling event has not been described for signaling through ICAM-1. Here, tyrosine phosphorylation of cellular proteins was examined after cross-linking of ICAM-1. Tyrosine phosphorylation of the 34-kDa cdc2 protein kinase was induced transiently after stimulation of the leukemic T cell line, Molt-3, or peripheral blood T cells. Stimulation through ICAM-1 had no effect on constitutive presence of cdc2 or phosphorylation of cdc2 on threonine. cdc2 kinase activity was constitutive in peripheral blood T cells, and transient inhibition of kinase activity after ICAM-1 stimulation correlated kinetically with phosphorylation of cdc2 on tyrosine. ...
Receptor Tyrosine Protein Kinase ERBB 3 (Proto Oncogene Like Protein c ErbB 3 or Tyrosine Kinase Type Cell Surface Receptor HER3 or HER3 or ERBB3 or EC - Drugs in Development, 2021 provides in depth analysis on Receptor Tyrosine Protein Kinase ERBB 3 (Proto Oncogene Like Protein c ErbB 3 or Tyrosine Kinase Type Cell Surface Receptor HER3 or HER3 or ERBB3 or EC targeted pipeline therapeutics. The report provides comprehensive information complete with Analysis by Indications, Stage of Development, Mechanism of Action (MoA), Route of Administration (RoA) and Molecule Type. The report also covers the descriptive pharmacological action of the therapeutics, its complete research and development history and latest news and press releases. Additionally, the report provides an overview of key players involved in Receptor Tyrosine Protein Kinase ERBB 3 (Proto Oncogene Like Protein c ErbB 3 or Tyrosine Kinase Type Cell Surface Receptor HER3 or HER3 or ERBB3 or EC targeted ...
CD20 is a B cell-specific 35/37 kDa integral membrane protein which modulates proliferation and differentiation of normal resting B cells when stimulated by CD20 antibodies. An increase in c-myc mRNA levels occurs within hours after treatment of resting B cells with CD20 mAb; however earlier events in the CD20 signal transduction pathway have not been described. Here we demonstrate that anti-CD20 mediated induction of c-myc mRNA is inhibited by the tyrosine kinase inhibitor herbimycin A, that CD20 is associated with both tyrosine and serine kinase activity, and that tyrosine phosphorylation of multiple substrates is induced within minutes upon ligation of CD20 with mAb. Association of the tyrosine and serine kinases with CD20 was stable in lysis buffer containing 1% NP40 and 0.25% deoxycholate. Under the same conditions, antibodies against several other B cell surface molecules failed to co-precipitate tyrosine kinase activity, however, a serine kinase was precipitated by the anti-CD19 mAb, B43. ...
Introduction: : Previously we demonstrated that trinucleotides released from the wound stimulate purinergic receptors and elicit a complex signaling cascade that ultimately mediates wound closure. Purpose: : Our goal is to evaluate the role and activation of the epidermal growth factor receptor (EGFR) tyrosine residues that occur in response to injury induced purinergic receptor activation. Methods: : Primary corneal epithelial cells and HCE-Ts were used for evaluation. Calcium signaling was monitored using live cell confocal imaging with a perfusion system. Phosphorylation and localization of specific EGFR tyrosine residues was assessed using immunohistochemistry, confocal microscopy and western blot analysis. The EGFR was downregulated using a kinase inhibitor AG1478 or siRNA. Results: : We have demonstrated that downregulation of EGFR via siRNA or kinase inhibitors reduces injury induced ERK phosphorylation. Injury induced a differential phosphorylation of the EGFR on tyrosine residues,1068, ...
The Src-family and Syk/ZAP-70 family of protein tyrosine kinases (PTK) are required for T cell receptor (TCR) functions. We provide evidence that the Src-family PTK Lck is responsible for regulating the constitutive tyrosine phosphorylation of the TCR zeta subunit in murine thymocytes. Moreover, ligation of the TCR expressed on thymocytes from Lck-deficient mice largely failed to induce the phosphorylation of TCR-zeta, CD3 epsilon, or ZAP-70. In contrast, we find that the TCR-zeta subunit is weakly constitutively tyrosine phosphorylated in peripheral T cells isolated from Lck-null mice. These data suggest that Lck has a functional role in regulation of TCR signal transduction in thymocytes. In peripheral T cells, other Src-family PTKs such as Fyn may partially compensate for the absence of Lck. ...
TY - JOUR. T1 - A new method for isolating tyrosine kinase substrates used to identify Fish, an SH3 and PX domain-containing protein, and Src substrate. AU - Lock, Peter. AU - Abram, Clare L.. AU - Gibson, Toby. AU - Courtneidge, Sara A.. PY - 1998/8/3. Y1 - 1998/8/3. N2 - We describe a method for identifying tyrosine kinase substrates using anti-phosphotyrosine antibodies to screen tyrosine-phosphorylated cDNA expression libraries. Several potential Src substrates were identified including Fish, which has five SH3 domains and a recently discovered phox homology (PX) domain. Fish is tyrosine-phosphorylated in Src-transformed fibroblasts (suggesting that it is a target of Src in vivo) and in normal cells following treatment with several growth factors. Treatment of cells with cytochalasin D also resulted in rapid tyrosine phosphorylation of Fish, concomitant with activation of Src. These data suggest that Fish is involved in signalling by tyrosine kinases, and imply a specialized role in the ...
In the second post on ADHD and tyrosine, we focused on the first step of the process, the conversion of tyrosine to L-DOPA. This step heavily utilizes a specific enzyme called tyrosine hydroxylase. Tyrosine Hydroxylase is dependent on adequate supplies of certain nutrients such as iron, magnesium, zinc, tetrahydrobiopterin, and adequate levels of vitamin C (and antioxidants in general). While rampant supplementation is not necessary, inadequate levels of any of these agents (as well as a few others, such as copper) could potentially compromise the function of the tyrosine hydroxylase enzyme. It is important to note that the conversion of tyrosine to L-DOPA is typically the slowest and rate-limiting step of the whole tyrosine metabolism and conversion process to dopamine and norepinephrine. Thus, compromising this first conversion step can be potentially the most devastating with regards to impaired tyrosine metabolism for ADHD. This was why the post was a bit lengthy with regards to advocating ...
The conditions of the cellular microenvironment in complex multicellular organisms fluctuate, enforcing permanent adaptation of cells at multiple regulatory levels. Covalent post-translational modifications of proteins provide the short-term response tools for cellular adjustment and growing evidence supports the possibility that protein tyrosine nitration is part of this cellular toolkit and not just a marker for oxidative damage. We have demonstrated that protein tyrosine nitration fulfils the major criteria for signalling and suggest that the normally highly regulated process may lead to disease upon excessive or inappropriate nitration.. ...
Full signaling from the T cell receptor (TCR) requires the presence of the linker for activation of T cells (LAT) protein. Human LAT contains 10 tyrosine residues, of which at least five reside in appropriate amino acid sequence contexts that may associate with phosphotyrosine-binding proteins. Lin and Weiss identified the tyrosine residues on LAT required for proper TCR-dependent calcium mobilization and mitogen-associated protein kinase (MAPK) activation. Tyr132, Tyr171, and Tyr191 together were responsible for mediating normal amounts of calcium flux; the presence of one, but not all, of these tyrosines drastically reduced calcium mobilization. Full MAPK activation required the presence of Tyr110 and Tyr226. In addition, Lin and Weiss found that full MAPK and calcium activation required the critical tyrosine residues to be fully present on individual LAT proteins; mutant LAT proteins containing some, but not all, of the essential tyrosines could not activate MAPK or calcium responses. Thus, ...
Supplementary MaterialsSupplementary Document. phosphorylated at tyrosine 97 in the postischemic mind upon neuroprotective insulin treatment, but how such posttranslational changes affects mitochondrial rate of metabolism is unclear. Here, we report the structural features and functional behavior of a phosphomimetic cytochrome mutant, which was generated by site-specific incorporation at position 97 of oxidase, or complex IV, within respiratory supercomplexes was higher than that of the wild-type species, in agreement with the observed decrease in reactive oxygen species production. Direct contact of cytochrome with the respiratory supercomplex factor HIGD1A (hypoxia-inducible domain family member 1A) is reported here, with the mutant heme protein exhibiting a lower affinity than the wild-type species. Interestingly, phosphomimetic cytochrome also exhibited a lower caspase-3 activation activity. Altogether, these findings yield a better understanding of the molecular basis for mitochondrial ...
A major mechanism of injury associated with the production of nitric oxide (NO*) in vivo is due to its diffusion-limited reaction with superoxide to form peroxynitrite, which in turn may cause nitration of protein tyrosine residues. To assess the physiological role of tyrosine nitration, it is cruci …
Chemokines are secreted proteins that direct the migration of immune cells and are involved in numerous disease states. For example, CCL21 (CC chemokine ligand 21) and CCL19 (CC chemokine ligand 19) recruit antigen-presenting dendritic cells and naïve T-cells to the lymph nodes and are thought to play a role in lymph node metastasis of CCR7 (CC chemokine receptor 7)-expressing cancer cells. For many chemokine receptors, N-terminal posttranslational modifications, particularly the sulfation of tyrosine residues, increases the affinity for chemokine ligands and may contribute to receptor ligand bias. Chemokine sulfotyrosine (sY) binding sites are also potential targets for drug development. In light of the structural similarity between sulfotyrosine and phosphotyrosine (pY), the interactions of CCL21 with peptide fragments of CCR7 containing tyrosine, pY, or sY were compared using protein NMR (nuclear magnetic resonance) spectroscopy in this study. Various N-terminal CCR7 peptides maintain binding site
TY - JOUR. T1 - Proteinuria and hypertension with tyrosine kinase inhibitors. AU - Kandula, Praveen. AU - Agarwal, Rajiv. PY - 2011/12/2. Y1 - 2011/12/2. N2 - Tyrosine kinases are important for the development of pathological angiogenesis, a critical factor for survival and proliferation of tumor cells. Inhibition of tyrosine kinases either through targeted binding of its ligands or inhibition of its receptor has led to significant hindrance in angiogenesis and has improved survival for several cancers. Several of these antibodies or small molecules have been approved for treatment of recurrent and resistant cancers over the last decade. Although generally well tolerated, tyrosine kinase inhibitors have been linked with development of hypertension and proteinuria. We review the literature for incidence and severity of hypertension and proteinuria among several tyrosine kinase inhibitors, their pathophysiologic mechanisms, and provide a guide for screening and management.. AB - Tyrosine kinases ...
Results Western blot analyses with three different antibodies against phosphotyrosine revealed that pp68 and pp125 were the two major tyrosine-phosphorylated proteins present in the normal carotid artery and the aorta. Reprobing with various antibodies identified these proteins was paxi1lin and FAK. Immunodepletion with antiphosphotyrosine removed FAK and paxillin, which suggested that most of these proteins were tyrosinephosphorylated in the artery. The artery contained greater amount of tyrosine-phosphorylated FAK than that in the other tissues examined, including the inferior vena cava and the heart. The content of FAK and paxillin was decreased following the balloon injury of the carotid artery, but not after endothelial denudation ex vivo.. ...
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.. Tyrosine kinases play a prominent role in human cancer, yet the oncogenic signaling pathways driving cell proliferation and survival have been difficult to identify, in part because of the complexity of the pathways and in part because of low cellular levels of tyrosine phosphorylation. In general, global phosphoproteomic approaches reveal small numbers of peptides containing phosphotyrosine. We have developed a strategy that emphasizes the phosphotyrosine component of the phosphoproteome and identifies large numbers of tyrosine phosphorylation sites. Peptides containing phosphotyrosine are isolated directly from protease-digested cellular protein extracts with a phosphotyrosine-specific antibody and are identified by tandem mass spectrometry. Applying this approach to several cell systems, including cancer cell lines, shows it can be used to identify activated protein kinases and their ...
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Adaptor protein c-Abl SH3 domain-binding protein-2 (3BP2) is known to play regulatory roles in immunoreceptor-mediated signal transduction. We have previously demonstrated that Tyr{sup 174}, Tyr{sup 183} and Tyr{sup 446} in mouse 3BP2 are predominantly phosphorylated by Syk, and the phosphorylation of Tyr{sup 183} and the Src homology 2 (SH2) domain of mouse 3BP2 are critical for B cell receptor (BCR)-induced activation of nuclear factor of activated T cells (NFAT) in human B cells. In this report, we have shown that Syk, but not Abl family protein-tyrosine kinases, is critical for BCR-mediated tyrosine phosphorylation of 3BP2 in chicken DT40 cells. Mutational analysis showed that Tyr{sup 174}, Tyr{sup 183} and Tyr{sup 426} of chicken 3BP2 are the major phosphorylation sites by Syk and the SH2 domain of 3BP2 is critical for tyrosine phosphorylation. In addition, phosphorylation of Tyr{sup 426} is required for the inducible interaction with the SH2 domain of Vav3. Moreover, the expression of the ...
by Chalita Washington, Rachel Chernet, Rewatee H. Gokhale, Yesenia Martino-Cortez, Hsiu-Yu Liu, Ashley M. Rosenberg, Sivan Shahar, Cathie M. Pfleger. Dysregulation of the Ras oncogene in development causes developmental disorders, Rasopathies, whereas mutational activation or amplification of Ras in differentiated tissues causes cancer. Rabex-5 (also called RabGEF1) inhibits Ras by promoting Ras mono- and di-ubiquitination. We report here that Rabex-5-mediated Ras ubiquitination requires Ras Tyrosine 4 (Y4), a site of known phosphorylation. Ras substitution mutants insensitive to Y4 phosphorylation did not undergo Rabex-5-mediated ubiquitination in cells and exhibited Ras gain-of-function phenotypes in vivo. Ras Y4 phosphomimic substitution increased Rabex-5-mediated ubiquitination in cells. Y4 phosphomimic substitution in oncogenic Ras blocked the morphological phenotypes associated with oncogenic Ras in vivo dependent on the presence of Rabex-5. We developed polyclonal antibodies raised ...
Diabetes mellitus is commonly considered as a disease of a scant beta-cell mass that fails to respond adequately to the functional demand. Tyrosine kinases may play a role for beta-cell replication, differentiation (neoformation) and survival. Transfection of beta-cells with DNA constructs coding for tyrosine kinase receptors yields a ligand-dependent increase of DNA synthesis in beta-cells. A PCR-based technique was adopted to assess the repertoire of tyrosine kinases expressed in fetal islet-like structures, adult islets or RINm5F cells. Several tyrosine kinase receptors, such as the VEGFR-2 (vascular endothelial growth factor receptor 2) and c-Kit, were found to be present in pancreatic duct cells. Because ducts are thought to harbor beta-cell precursor cells, these receptors may play a role for the neoformation of beta-cells. The Src-like tyrosine kinase mouse Gtk (previously named Bsk/Iyk) is expressed in islet cells, and was found to inhibit cell proliferation. Furthermore, it conferred ...
Protein-tyrosine kinases (PTKs) catalyze the transfer of the γ-phosphate of ATP to tyrosine residues of protein substrates, are critical components of signaling pathways that control cellular proliferation and differentiation. Two classes of PTKs are present in cells: the transmembrane receptor PTKs and the nonreceptor PTKs.. The RTK family includes the receptors for insulin and for many growth factors, such as EGF, FGF, PDGF, VEGF, and NGF. RTKs are transmembrane glycoproteins that are activated by the binding of their ligands, and they transduce the extracellular signal to the cytoplasm by phosphorylating tyrosine residues on the receptors themselves (autophosphorylation) and on downstream signaling proteins. RTKs activate numerous signaling pathways within cells, leading to cell proliferation, differentiation, migration, or metabolic changes. In addition, nonreceptor tyrosine kinases (NRTKs), which include Src, JAKs, and Abl, among others, are integral components of the signaling cascades ...
[111 Pages Report] Check for Discount on Receptor Tyrosine Protein Kinase ERBB 4 (Tyrosine Kinase Type Cell Surface Receptor HER4 or Proto Oncogene Like Protein c ErbB 4 or p180erbB4 or HER4 or ERBB4 or EC - Pipeline Review, H1 2016 report by Global Markets Direct. Global Markets Directs, Receptor Tyrosine Protein Kinase ERBB 4 (...
TY - JOUR. T1 - Ron is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP. AU - Gaudino, Giovanni. AU - Follenzi, Antonia. AU - Naldini, Luigi. AU - Collesi, Chiara. AU - Santoro, Massimo. AU - Gallo, Kathleen A.. AU - Godowski, Paul J.. AU - Comoglio, Paolo M.. PY - 1994. Y1 - 1994. N2 - RON, a cDNA homologous to the hepatocyte growth factor (HGF) receptor gene (MET), encodes a putative tyrosine kinase. Here we show that the RON gene is expressed in several epithelial tissues as well as in granulocytes and monocytes. The major RON transcript is translated into a glycosylated single chain precursor, cleaved into a 185 kDa heterodimer (p185(RON)) of 35 (α) and 150 kDa (β) disulfide-linked chains, before exposure at the cell surface. The Ron,β-chain displays intrinsic tyrosine kinase activity in vitro, after immunoprecipitation by specific antibodies. In vivo, tyrosine phosphorylation of p185(RON) is induced by stimulation with macrophage stimulating protein (MSP), a ...
Formation of 3-Nitrotyrosine During Oxidative Stress. An increase in the presence of nitrotyrosine is correlated with an increase in the presence of nitric oxide (NO).. ...
W. P. T. James, P. J. Garlick, P. M. Sender; Studies of Protein Metabolism in Man with Infusions of [14C]Tyrosine. Clin Sci Mol Med 1 January 1974; 46 (1): 8P. doi: https://doi.org/10.1042/cs046008Pa. Download citation file:. ...
RTK BRET-2 Assays Are Dependent on Autophosphorylation of Specific Tyrosine Residues. Phosphorylated tyrosine residues localized in the intracellular carboxyl terminus of EGFR (Heldin, 1995) and specific phosphotyrosine binding or SH2 domains in the effector proteins (Schlessinger and Lemmon, 2003) mediate all the EGFR effector interactions we studied in Fig. 2. EGFR tyrosines 1068, 1086, 1101, 1114, 1148, and 1173 are involved in direct or indirect binding of the effector Grb2 (Schulze et al., 2005). We mutated these tyrosine residues to phenylalanine to verify that the EGFR/Grb2 BRET-2 signal is dependent on their phosphorylation. Introducing all six Tyr-to-Phe alterations into EGFR-Luc abolished the EGF-induced BRET-2/Grb2 response by 90 ± 0.9% compared with wild-type EGFR-Luc (Fig. 2f). We observed 66 ± 0.9% and 42 ± 1.0% impairment of the BRET-2/Grb2 responses for EGFR-Luc isoforms carrying five (Y1068F, Y1086F, Y1101F, Y1114F, Y1173F) or four (Y1086F, Y1101F, Y1114F, Y1173F) of the six ...
The growth, differentiation and functions of immune and hematopoietic cells are controlled by multiple cytokines, including interleukins (ILs) and colony stimulating factors (CSFs). Cytokines exert their biological effects through binding to cell‐surface receptors that are associated with one or more members of the JAK family of cytoplasmic tyrosine kinases (JAKs). Cytokine‐induced receptor dimerization leads to the activation of JAKs, rapid tyrosine phosphorylation of the cytoplasmic domains and subsequent recruitment of various signaling proteins to the receptor complex (Ihle, 1995). Among these proteins are members of the signal transduction and activators of transcription (STAT) family (Ihle, 1996; Darnell, 1997; OShea, 1997). The tyrosine‐phosphorylated STATs form homo‐ or heterodimers and translocate into the nucleus, they then activate target genes.. The regulation of the JAKs is a central component in the regulation of cytokine signaling. Because of the critical role of ...
Receptor tyrosine kinases have an individual transmembrane (TM) section thats usually assumed to try out a passive function in ligand-induced dimerization and activation from the receptor. and covalent cross-linking tests. Our findings tension the part of TM website relationships in ErbB receptor function, and perhaps for additional single-spanning membrane protein. Intro Receptor tyrosine kinases (RTKs) are transmembrane (TM) glycoproteins that contain a adjustable extracellular N-terminal website, an individual membrane spanning domains, and a big Mdk cytoplasmic portion made up of a juxtamembrane domains, the extremely conserved tyrosine kinase domains, and a C-terminal regulatory area. Biochemical and structural data concur in todays proven fact that ligand binding stimulates monomeric receptor dimerization and trans-autophosphorylation at described tyrosine residues through intrinsic kinase activity (Heldin, 1995 ; Weiss and Schlessinger, 1998 ; Hubbard, 1999 ). Whereas ligand-induced RTK ...
Thrombin-induced accumulation of phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4)P2) but not of PtdIns(3,4,5,)P3 is strongly correlated with the relocation to the cytoskeleton of 29% of the p85 alpha regulatory subunit of phosphoinositide 3-kinase (PtdIns 3-kinase) and is accompanied by a significant increase in PtdIns 3-kinase activity in this subcellular fraction. Actually, PtdIns(3,4)P2 accumulation and PtdIns 3-kinase, pp60c-src, and p125FAK translocations as well as aggregation were concomitant events occurring with a distinct lag after actin polymerization. The accumulation of PtdIns(3,4)P2 and the relocalization of PtdIns 3-kinase to the cytoskeleton were both dependent on tyrosine phosphorylation, integrin signaling, and aggregation. Furthermore, although p85 alpha was detected in anti-phosphotyrosine immunoprecipitates obtained from the cytoskeleton of thrombin-activated platelets, we failed to demonstrate tyrosine phosphorylation of cytoskeletal p85 alpha. Tyrphostin treatment ...
The development of monoclonal antibodies (mAbs) that recognize nearly all of the phosphorylated tyrosine residues, irrespective of the surrounding sequences, enables researchers to detect the phosphorylation state of proteins through the use of anti-phosphotyrosine western blotting. The availability of this simple, reliable, nonradioactive and yet sensitive method created a boom in signal transduction research. While the methodology of how to perform an anti-phosphotyrosine western blot remains unchanged since the procedure became widely used in the early part of 1990s, steady improvements in reagents and detection technologies have allowed researchers to detect tyrosine phosphorylation quantitatively, at unprecedented sensitivity. In addition to the improvements in the western blot-based systems, powerful new phosphotyrosine detection platforms, based on proteomic technologies, are emerging rapidly. This unit will describe in detail the steps needed to perform the standard anti-phosphotyrosine ...
Press Release issued Jul 9, 2018: Tyrosine kinases are enzymes capable of transferring the phosphate group from ATP (adenosine triphosphate) to a cellular protein. They function as an on or off switch for several cellular mechanisms. On the protein, the phosphate group is affiliated to the tyrosine amino acid. Tyrosine kinases are a subclass of the larger group of protein kinases that connect phosphate groups to extra amino acids (threonine and serine). In interconnecting signals in a cell (signal transduction) and cellular activities such as cell division regulation, proteins phosphorylation is an important mechanism, which is performed by kinases.
In unstimulated cells, the STAT proteins are inactive and are localized to cytoplasm. The binding of ligand to the receptor leads to the activation of JAK. The function of JAK is activated and being a tyrosine kinase, it phosphorylates the tyrosine residues on the receptor. As a result, the sites for phosphotyrosine-binding of SH2 domains is created. As mentioned above that STAT proteins have SH2 domains and hence these proteins are recruited to bind to phosphotyrosine residues via SH2 domain. These STATs are now phosphorylated on their tyrosine residues by JAKs. These phosphorylated tyrosine now act as a binding site for SH2 domains of other STATs. This leads to dimerization of STAT proteins. STATs can form homodimers or heterodimers. These dimers then translocates to the cell nucleus where they stimulate the activation of the target genes ...
Tyrosine Info! The brain converts Tyrosine to the stimulatory neurotransmitter dopamine, norepinephrine, and epinephrine (the last two being the famous fight or flight hormones), known collectively as catecholamines. Ordinary tyrosine is less stable and is insoluble in water, which may result in reduced bioavailability. Acetylation enhances the solubility and stability of certain amino acids.. In short, the evidence is strong that supplemental tyrosine can improve performance as well as increase energy levels, along with a host of other subjective feelings of mental ability and well-being.. ...
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Int. J. Mol. Sci. 2011, 12, 3740-3756; doi:10.3390/ijms12063740. OPEN ACCESS. International Journal of. Molecular Sciences. ISSN 1422-0067. www.mdpi.com/journal/ijms. Article. Sulfotyrosine Recognition as Marker for Druggable Sites in the Extracellular Space. 11 2 1. Joshua J. Ziarek , Maxime S. Heroux , Christopher T. Veldkamp , Francis C. Peterson. and Brian F. Volkman. 1 Department of Biochemistry, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA; E-Mails: [email protected] (J.J.Z.); [email protected] (M.S.H.); [email protected] (F.C.P.). Department of Chemistry, University of Wisconsin-Whitewater, 800 West Main Street, Whitewater, WI 53190, USA; E-Mail: [email protected] * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +1-414-955-8400; Fax: +1-414-955-6510.. Received: 14 March 2011; in revised form: 16May 2011 /Accepted: 23 May 2011 /. Published: 8 June 2011. Abstract: Chemokine signaling is a well-known agent of autoimmune ...
Tyrosine sulfation Tyrosine sulfation is a posttranslational modification where a sulfate group is added to a tyrosine residue of a protein molecule. Secreted
TYROSINE Tyrosine refers to the class called amino acids the building blocks of the structural component of body i.e. proteins. Human body get its tyrosine from another amino acid the phenylalanine. It is also the main constituent of dairy products, fish, nuts, meat, eggs, wheat and oats. Tyrosine is the man constituent of protein supplements […]. ...
TY - JOUR. T1 - Cross-linking of tyrosine-containing peptides by hydrogen peroxide-activated Coprinus Cinereus peroxidase. AU - Steffensen, C.L.. AU - Mattinen, Maija-Liisa. AU - Andersen, Henrik Jørgen. AU - Kruus, Kristiina. AU - Buchert, Johanna. AU - Holm Nielsen, Jacob. PY - 2008. Y1 - 2008. N2 - Hydrogen peroxide-activated Coprinus Cinereus peroxidase (CIP) can initiate polymerization of tyrosine-containing peptides via initial formation of an intermediate tyrosyl radical, which for the first time has been identified by spin trap electron spin resonance spectroscopy as located on carbon 1 in the aromatic ring, and subsequent formation of either dityrosine or isodityrosine bonds through a net elimination of two hydrogen atoms between peptides. The rate and degree of polymerization were found to depend on peptide size and the amino acid adjacent to tyrosine, as longer peptides and amino acids with bulky side groups were less reactive. In the forwarded hypothesis for the reaction mechanism ...
Erratum: Mutagenesis of T cell antigen receptor ζ chain tyrosine residues. Effects on tyrosine phosphorylation and lymphokine production (Journal of Biological Chemistry (1992) 267 (13656-13660 ...
Proliferation and migration of SMCs in the arterial wall play pivotal roles in atherosclerosis and restenosis.1,28 In the present study, we demonstrate for the first time that balloon injury in arteries and PDGF in cultured SMCs stimulate the tyrosine phosphorylation of c-Cbl. We also show that the c-Cbl mutant, which is deficient in the major tyrosine phosphorylation sites, attenuates the activation of the Akt/mTOR pathway and inhibits SMC migration and proliferation in response to PDGF, FGF, and serum. Finally, we demonstrate that in vivo gene transfer of the c-Cbl mutant inhibits SMC proliferation and migration in vivo and prevents neointimal hyperplasia after balloon injury.. c-Cbl undergoes tyrosine phosphorylation in response to a multitude of stimuli, including activated growth factor receptor protein tyrosine kinases (PTKs; such as epidermal growth factor receptor, FGFR, and PDGFR), cytokines, hormones, and mechanical stimuli (such as shear stress). We describe here that c-Cbl undergoes ...
The role of fibroblast growth factor-2 (FGF-2) in maintaining undifferentiated human embryonic stem cells (hESC) was investigated using a targeted phosphoproteomics approach to specifically profile tyrosine phosphorylation events following FGF-2 stimulation. A cumulative total number of 735 unique tyrosine phosphorylation sites on 430 proteins were identified, by far the largest inventory to date for hESC. Early signaling events in FGF-2 stimulated hESC were quantitatively monitored using stable isotope dimethyl labeling, resulting in temporal tyrosine phosphorylation profiles of 316 unique phosphotyrosine peptides originating from 188 proteins. Apart from the rapid activation of all four FGF receptors, trans-activation of several other receptor tyrosine kinases (RTKs) was observed as well as induced tyrosine phosphorylation of downstream proteins such as PI3-K, MAPK and several Src family members. Both PI3-K and MAPK have been linked to hESC maintenance through FGF-2 mediated signaling. The ...
In this report, we investigated the role of tyrosine phosphorylation of JAK3 in regulating its kinase activity. We first provide evidence that JAK3 has multiple autophosphorylation sites and that both Y980 and Y981, within the putative activation loop of JAK3, are phosphorylated. We found that Y980 is required for efficient phosphorylation of Y981 and other tyrosines within JAK3. Phosphorylation of 980 was also critical for phosphorylation of γc and STAT5A. In contrast, mutation of Y981 increases JAK3 activity and thus may be a negative regulatory site.. It is well recognized that JAK activation is associated with its own phosphorylation on tyrosine residues in the JAK/STAT signal transduction pathway, but it is less clear precisely how JAKs become activated (5-7). Upon ligand binding, JAK activation, which occurs as a results of receptor dimerization/oligomerization, is thought to involve auto- or trans-phosphorylation by another JAK. This leads to kinase activation, resulting in ...
We have examined the effects of the protein tyrosine phosphatase inhibitor pervanadate on activation of signal transduction in human umbilical vein endothelial cells. Endothelial cells responded to pervanadate treatment by increasing tyrosine phosphorylation of cellular proteins, including phospholipase C (PLC) gamma 1, generating inositol phosphates (IPs), releasing arachidonic acid, and producing prostacyclin (prostaglandin [PG] I2). The dose and time responses for these events were similar. Tyrosine phosphorylation and formation of IPs in response to pervanadate were reduced by both staurosporine and genistein. Short-term incubation with the phorbol ester 12-O-tetradecanoylphorbol 13-acetate, which inhibits thrombin-induced IP generation, did not affect the IP response to pervanadate. To investigate the possible involvement of tyrosine phosphorylation in thrombin or histamine-induced IP generation and PGI2 production, we examined the effects of costimulation with pervanadate and either ...
TY - JOUR. T1 - Hepatic tyrosine-phosphorylated proteins identified and localized following in vivo inhibition of protein tyrosine phosphatases. T2 - effects of H2O2 and vanadate administration into rat livers. AU - Hadari, Yaron R.. AU - Geiger, Benjamin. AU - Nadiv, Orna. AU - Sabanay, Ilana. AU - Roberts, Charles T.. AU - LeRoith, Derek. AU - Zick, Yehiel. PY - 1993/11. Y1 - 1993/11. N2 - Injection of a combination of H2O2 and vanadate (H/V) into the portal vein of rat livers resulted in inhibition of protein tyrosine phosphatase activity and led to a dramatic enhanced in vivo protein tyrosine phosphorylation. Some of the phosphorylated proteins were identified as the β-subunit of the insulin receptor, the insulin receptor substrate 1 (ppl85), PLC-γ (pp145), and a 100 kDa PLC-γ-associated protein. Immunofluorescense and immune electron microscopy of frozen liver sections with anti-P-Tyr antibodies revealed that most of the tyrosine-phosphorylated proteins are localized in close proximity ...
The N-methyl-D-aspartate receptor (NMDAR) is an ionotropic glutamate receptor, which plays crucial roles in synaptic plasticity and development. We have recently shown that potentiation of NMDA receptor function by protein kinase C (PKC) appears to be mediated via activation of non-receptor tyrosine kinases. The aim of this study was to test whether this effect could be mediated by direct tyrosine phosphorylation of the NR2A or NR2B subunits of the receptor. Following treatment of rat hippocampal CA1 mini-slices with 500 nM phorbol 12-myristate 13-acetate (PMA) for 15 min, samples were homogenized, immunoprecipitated with anti-NR2A or NR2B antibodies and the resulting pellets subjected to Western blotting with antiphosphotyrosine antibody. An increase in tyrosine phosphorylation of both NR2A (76 +/- 11% above control) and NR2B (41 +/- 11%) was observed. This increase was blocked by pretreatment with the selective PKC inhibitor chelerythrine, with the tyrosine kinase inhibitor Lavendustin A or with the
We have used unbiased phosphoproteomic approaches, based on quantitative mass spectrometry using stable isotope labeling with amino acids in cell culture (SILAC), to identify tyrosine phosphorylated proteins in isogenic human bronchial epithelial cells (HBECs) and human lung adenocarcinoma cell lines, expressing either of the two mutant alleles of EGFR (L858R and Del E746-A750), or a mutant KRAS allele, which are common in human lung adenocarcinomas. Tyrosine phosphorylation of signaling molecules was greater in HBECs expressing the mutant EGFRs than in cells expressing WT EGFR or mutant KRAS. Receptor tyrosine kinases (such as EGFR, ERBB2, MET, and IGF1R), and Mig-6, an inhibitor of EGFR signaling, were more phosphorylated in HBECs expressing mutant EGFR than in cells expressing WT EGFR or mutant RAS. Phosphorylation of some proteins differed in the two EGFR mutant-expressing cells; for example, some cell junction proteins (β-catenin, plakoglobin, and E-cadherin) were more phosphorylated in ...
In src- and ras-transformed cells, tyrosine phosphorylation of adherens junction (AJ) components is related to impairment of cell-cell adhesion. In this paper we report that in human endothelial cells (EC), tyrosine phosphorylation of AJ can be a physiological process regulated by cell density. Immunofluorescence analysis revealed that a phosphotyrosine (P-tyr) antibody could stain cell-cell junctions only in sparse or loosely confluent EC, while the staining was markedly reduced in tightly confluent cultures. This process was reversible, since on artificial wounding of EC monolayers, the cells at the migrating front reacquired P-tyr labelling at cell contacts. In EC, the major cadherin at intercellular AJ is the cell-type-specific VE-cadherin. We therefore analyzed whether this molecule was at least in part responsible for the changes in P-tyr content at cell junctions. Tyrosine phosphorylation of VE-cadherin, beta-catenin and p120, occurred in looser AJ, i.e. in recently confluent cells, and ...
CSFR an oncogenic tyrosine kinase receptor for CSF-1 (M-CSF). Drives growth and development of monocytes. Binding of CSF-1 induces receptor dimerization, activation and autophosphorylation of cytoplasmic tyrosine residues used as docking sites for SH2-containing signaling proteins. There are at least five major tyrosine autophosphorylation sites. Two point mutations seen in 10-20% of patients with acute myeloid leukemia, chronic myelomonocytic leukemia or myelodysplasia. One mutation appears to be both somatic and germline, and disrupts Cbl binding and receptor turnover. v-fms lacks the Cbl binding site and causes feline leukemia. Mutations may also develop after chemotherapy for lymphoma. A distinct point mutation was found in some cases of hepatocellular carcinoma and related to increased expression, and another mutation was found in 2 of 40 patients with idiopathic myelofibrosis. Expression is elevated in breast tumors and cell lines, and expression in xenografts and transgenic mice has been ...
Abstract: Tyrosine hydroxylase activity was measured under optimal and suboptimal assay conditions in hippocampal extracts from young (2 month), mature (12 month), and old (24 month) Fischer 344 male rats 72 h after the infusion of 200 µg of the neurotoxin 6-hydroxydopamine or vehicle into the lateral ventricle. The lesion resulted in a 45-55% decrease of tyrosine hydroxylase activity measured under optimal conditions (pH 6.1, 3.0 mM 6-methyl-5,6,7,8-tetrahydropterin) and an ∼35% decrease in the relative concentration of immunoreactive tyrosine hydroxylase. When measured under suboptimal conditions (pH 6.6, 0.7 mM 6-methyl-5,6,7,8-tetrahydropterin), tyrosine hydroxylase activity in 2- and 12-month-old lesioned animals was twice that measured in vehicle-treated animals. However, in the old lesioned animals, tyrosine hydroxylase activity measured under suboptimal conditions was not different from that measured in age-matched vehicle-treated animals. Isoforms of tyrosine hydroxylase were ...
Ligand binding to cell surface receptors initiates a cascade of signaling events regulated by dynamic phosphorylation events on a multitude of pathway proteins. Quantitative features, including intensity, timing, and duration of phosphorylation of particular residues, may play a role in determining cellular response, but experimental data required for analysis of these features have not previously been available. To understand the dynamic operation of signaling cascades, we have developed a method enabling the simultaneous quantification of tyrosine phosphorylation of specific residues on dozens of key proteins in a time-resolved manner, downstream of epidermal growth factor receptor (EGFR) activation. Tryptic peptides from four different EGFR stimulation time points were labeled with four isoforms of the iTRAQ reagent to enable downstream quantification. After mixing of the labeled samples, tyrosine-phosphorylated peptides were immunoprecipitated with an anti-phosphotyrosine antibody and ...
STAT1 makes an essential contribution to innate immunity against viral and intramacrophagic bacterial disease. The objective of our study was to reveal any contribution of non‐tyrosine‐phosphorylated STAT1 to innate immunity. Examining cells and organs of mice expressing a Stat1Y701F mutant, the first observation of note was the strong dependence of STAT1 expression on its tyrosine phosphorylation through tonic signaling. None of the tested stimuli, including L. monocytogenes infection, caused upregulation of the Stat1 gene in the absence of its tyrosine‐phosphorylated product. Therefore, effects of the U‐Stat pathway as defined by Stark and colleagues which rely on an increase in STAT abundance could not be examined. In addition, any results obtained for the immune response of Stat1Y701F cells or mice could not be compared to WT counterparts because a distinction between effects of tyrosine phosphorylation and effects of STAT1 abundance was not possible. To overcome this problem, we ...
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In eukaryotes, protein tyrosine (Tyr) kinases (PTKs) control various cellular pathways such as gene expression, metabolism, cell growth and apoptosis, as well as membrane transport (Cowan‐Jacob, 2006). In bacteria, however, the physiological role of Tyr phosphorylation has just been revealed (Grangeasse et al, 2003). In fact, protein Tyr phosphorylation was initially thought to exist solely in eukaryotes (Levitzki and Gazit, 1995), and only since the last decade have researchers begun to investigate prokaryotic protein Tyr phosphorylation (Freestone et al, 1998; Grangeasse et al, 2007). So far, none of the PTK‐related structures determined have a prokaryotic source. Among the ∼20 PTKs characterized in Gram‐negative and Gram‐positive bacteria to date, all but three are homologues of Wzc/Etk (Cozzone et al, 2004; Grangeasse et al, 2007), the first and only extensively studied bacterial PTK family also known as bacterial Tyr (BY) kinases (Grangeasse et al, 2007).. Wzc/Etk PTKs are ...
Spickett, C. (Creator), Pitt, A. (Creator), Sousa, B. C. (Creator), Medeiros, R. (Creator) (15 Jan 2021). Identification and relative quantification of 3-nitrotyrosine residues in fibrinogen nitrated in vitro and fibrinogen from ischemic stroke patient plasma using LC-MS/MS. Aston Data Explorer. 10.17036/researchdata.aston.ac.uk.00000493 ...
An early biochemical event associated with T cell activation is tyrosine phosphorylation. We have previously shown that p56lck, a lymphocyte-specific protein tyrosine kinase, is hyperphosphorylated on serine and tyrosine residues 15 minutes after activation via CD2 with a concomitant shift to a higher molecular mass. We now demonstrate that the tyrosine kinase activity of p56lck is increased within seconds following CD2 triggering. This activity decreases thereafter correlating with the appearance of changes in phosphorylation previously described. These results suggest that p56lck may play an important role in the CD2 activation pathway.
TY - JOUR. T1 - Tyrosine phosphorylation controls Runx2-mediated subnuclear targeting of YAP to repress transcription. AU - Zaidi, Sayyed K.. AU - Sullivan, Andrew J.. AU - Medina, Ricardo. AU - Ito, Yoshiaki. AU - van Wijnen, Andre J. AU - Stein, Janet L.. AU - Lian, Jane B.. AU - Stein, Gary S.. PY - 2004/2/25. Y1 - 2004/2/25. N2 - Src/Yes tyrosine kinase signaling contributes to the regulation of bone homeostasis and inhibits osteoblast activity. Here we show that the endogenous Yes-associated protein (YAP), a mediator of Src/Yes signaling, interacts with the native Runx2 protein, an osteoblast-related transcription factor, and suppresses Runx2 transcriptional activity in a dose-dependent manner. Runx2, through its PY motif, recruits YAP to subnuclear domains in situ and to the osteocalcin (OC) gene promoter in vivo. Inhibition of Src/Yes kinase blocks tyrosine phosphorylation of YAP and dissociates endogenous Runx2-YAP complexes. Consequently, recruitment of the YAP co-repressor to ...
Montano X.. The nerve growth factor (NGF) receptor, trkA, the tumour suppressor p53 and the phosphatase SHP-1 are critical in cell proliferation and differentiation. SHP-1 is a trkA phosphatase that dephosphorylates trkA at tyrosines (Y) 674 and 675. p53 can induce trkA activation and tyrosine phosphorylation in the absence of NGF stimulation. In breast cancer tumours trkA expression is associated with increased patient survival. TrkA protein expression is higher in breast-cancer cell lines than in normal breast epithelia. In cell lines (but not in normal breast epithelia) trkA is functional and can be NGF-stimulated to promote cell proliferation. This study investigates the functional relationship between trkA, p53 and SHP-1 in breast-cancer, and reveals that in wild-type (wt) trkA expressing breast-cancer cells both endogenous wtp53, activated by therapeutic agents, and transfected wtp53 repress expression of SHP-1 through the proximal CCAAT sequence of the SHP-1-P1-promoter and the ...
Protein tyrosine phosphorylation controls many aspects of signaling in multicellular organisms. One of the major consequences of tyrosine phosphorylation is the creation of binding sites for proteins containing Src homology 2 (SH2) domains. To profile the global tyrosine phosphorylation state of the cell, we have developed proteomic binding assays encompassing nearly the full complement ofhuman SH2 domains. Here we provide a global view of SH2 domain binding to cellular proteins based on large-scale far-western analyses. We also use reverse-phase protein arrays to generate comprehensive, quantitative SH2 binding profiles for phosphopeptides, recombinant proteins, and entire proteomes. As an example, we profiled the adhesion-dependent SH2 binding interactions in fibroblasts and identified specific focal adhesion complex proteins whose tyrosine phosphorylation and binding to SH2 domains are modulated by adhesion. These results demonstrate that high-throughput comprehensive SH2 profiling provides valuable
Tyrosine Protein Kinase SYK - Pipeline Review, H2 2020 Summary Tyrosine Protein Kinase SYK (Spleen Tyrosine Kinase or p72 Syk or ...
Constitutive STAT3 activation by tyrosine phosphorylation of mutated or amplified tyrosine kinases (pYSTAT3) is critical for cancer initiation, progression, invasion, and motility of carcinoma cells. We showed that AF1q is associated with STAT3 signaling in breast cancer cells. In xenograft models, enhanced AF1q expression activated STAT3 and promoted tumor growth and metastasis in immunodeficient NSG mice. The cytokine secretory phenotype of MDA-MB-231LN breast cancer cells with altered AF1q expression revealed changes in expression of platelet-derived growth factor subunit B (PDGF-B). AF1q-induced PDGF-B stimulated motility, migration, and invasion of MDA-MB-231LN cells, and AF1q up-regulated platelet-derived growth factor receptor (PDGFR) signaling. Further, AF1q-induced PDGFR signaling enhanced STAT3 activity through Src kinase activation, which could be blocked by the Src kinase inhibitor PP1. Moreover, AF1q up-regulated tyrosine kinase signaling through PDGFR signaling, which was blockable by
Blog on Src, Autophosphorylation Site, Tyrosine Kinase Substrate substrate product: The Src, Autophosphorylation Site, Tyrosine Kinase Substrate n/a (Catalog #MBS639279) is a Substrate and ...
The mutant c-erbB-2 protein with Glu instead of Val-659 exhibited transforming activity in NIH 3T3 cells. This protein showed enhanced tyrosine kinase activity in vitro and enhanced autophosphorylation at Tyr-1248 located proximal to the carboxyl terminus. Enhanced tyrosine phosphorylation of several cellular proteins was detected in cells expressing the Glu-659 c-erbB-2 protein. Introduction of an additional mutation at the ATP-binding site (Lys-753 to Met) of this protein resulted in abolition of its transforming ability. These data indicate that the transforming potential of c-erbB-2 is closely correlated with elevated tyrosine kinase activity of the gene product. To investigate the role of autophosphorylation in cell transformation, we introduced an additional mutation at the autophosphorylation site of the Glu-659 c-erbB-2 protein (Tyr-1248 to Phe). This mutant protein exhibited lower tyrosine kinase activity and lower transforming activity. On the other hand, when the carboxyl-terminal 230 ...
The levels of tyrosine phosphorylation required for cell growth and differentiation are achieved through the coordinated action of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Depending upon the cellular context, these two types of enzymes may either antagonize or cooperate with each other during the signal transmission process. An imbalance between these enzymes may impair normal cell growth, leading to cellular transformation. Both PTKs and PTPs have evolved to a level of structural diversity that allows them to regulate many cellular processes. This review will focus on several specific examples that highlight the interplay between PTPs and PTKs in cell signaling.. ...
Thrombospondin-1 (TSP) induces endothelial cell (EC) actin reorganization and focal adhesion disassembly and influences multiple EC functions. To determine whether TSP might regulate EC-EC interactions, we studied the effect of exogenous TSP on the movement of albumin across postconfluent EC monolayers. TSP increased transendothelial albumin flux in a dose-dependent manner at concentrations ≥1 μg/ml (2.2 nM). Increases in albumin flux were observed as early as 1 h after exposure to 30 μg/ml (71 nM) TSP. Inhibition of tyrosine kinases with herbimycin A or genistein protected against the TSP-induced barrier dysfunction by >80% and >50%, respectively. TSP-exposed monolayers exhibited actin reorganization and intercellular gap formation, whereas pretreatment with herbimycin A protected against this effect. Increased staining of phosphotyrosine-containing proteins was observed in plaque-like structures and at the intercellular boundaries of TSP-treated cells. In the presence of protein tyrosine ...
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Pericellular proteolysis of the extracellular matrix by membrane type 1-matrix metalloproteinase (MT1-MMP) confers tumor cells with the ability to proliferate within three-dimensional (3D) matrices and sustains tumor growth in mice. In this study, we show that in addition to its matrix-degrading activity, phosphorylation of MT1-MMP on its unique tyrosine residue located within its cytoplasmic sequence (Tyr573) may also participate to these processes. Fibrosarcoma cells expressing a proteolytically active but non-phosphorylable mutant of MT1-MMP showed a markedly reduced proliferation rate when embedded within 3D type I collagen matrices, this antiproliferative effect being correlated with arrest in the G0/G1 phase of the cell cycle. Impaired tyrosine phosphorylation of MT1-MMP also inhibits anchorage-independent growth of HT-1080 cells in soft agar as well as their invasion of collagen barriers, two prominent attributes of tumor cells, suggesting a broad inhibitory effect of the MT1-MMP mutant ...
The interferon-alpha (IFN-alpha)-stimulated gene factor 3 (ISGF3), a transcriptional activator, contains three proteins, termed ISGF3 alpha proteins, that reside in the cell cytoplasm until they are activated in response to IFN-alpha. Treatment of cells with IFN-alpha caused these three proteins to be phosphorylated on tyrosine and to translocate to the cell nucleus where they stimulate transcription through binding to IFN-alpha-stimulated response elements in DNA. IFN-gamma, which activates transcription through a different receptor and different DNA binding sites, also caused tyrosine phosphorylation of one of these proteins. The ISGF3 alpha proteins may be substrates for one or more kinases activated by ligand binding to the cell surface and may link occupation of a specific polypeptide receptor with activation of transcription of a set of specific genes. ...
Leukocyte receptor tyrosine kinase is an enzyme that in humans is encoded by the LTK gene. The protein encoded by this gene is a member of the ALK/LTK receptor family of receptor tyrosine kinases (RTKs) whose ligand is unknown. Closely related to the insulin receptor family of RTKs. Tyrosine-specific phosphorylation of proteins is a key to the control of diverse pathways leading to cell growth and differentiation. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene. LTK has been shown to interact with IRS-1, Shc, and PIK3R1. GRCh38: Ensembl release 89: ENSG00000062524 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000027297 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. Maru Y, Hirai H, Takaku F (May 1990). Human ltk: gene structure and preferential expression in human leukemic cells. Oncogene Res. 5 (3): 199-204. PMID 2320375. Entrez Gene: LTK leukocyte tyrosine kinase. Lopes SS, Yang X, Müller J, ...
PTPases dephosphorylate growth factor receptors17,18⇓ and are considered among the most important regulators of signal transduction in tyrosine kinase-type receptors, including the insulin receptor and receptors for various growth factors.19,20⇓ PTPases have been shown to regulate the action, maturation, and phosphorylation of substrates of growth factor receptors.12,17,21,22⇓⇓⇓ PTPases include 2 categories. One consists of LAR and LRP, both of which have a receptor-like transmembrane structure and tandem conserved PTPase domains. The other type, cytosolic-type SHP2 (also known as SHPTP2, PTP1D, PTP2C, and Syp), contains 2 SH2 domains and 1 SH3 sequence.2,3,14⇓⇓ SHP2 binds to tyrosine kinases via its SH2 domains and is activated by phosphorylation of its tyrosine residue.4,23⇓ SHP2 also binds to IRS-1,7 as do other adapter proteins.11 SHP2 has been thought to positively influence intracellular signal transduction.24-27⇓⇓⇓ We have reported previously that SHP2 is expressed ...
Protein phosphorylation regulates a large variety of biological processes in all living cells. In pathogenic bacteria, the study of serine, threonine, and tyrosine (Ser/Thr/Tyr) phosphorylation has shed light on the course of infectious diseases, from adherence to host cells to pathogen virulence, replication, and persistence. Mass spectrometry (MS)-based phosphoproteomics has provided global maps of Ser/Thr/Tyr phosphosites in bacterial pathogens. Despite recent developments, a quantitative and dynamic view of phosphorylation events that occur during bacterial pathogenesis is currently lacking. Temporal, spatial, and subpopulation resolution of phosphorylation data is required to identify key regulatory nodes underlying bacterial pathogenesis. Herein, we discuss how technological improvements in sample handling, MS instrumentation, data processing, and machine learning should improve bacterial phosphoproteomic datasets and the information extracted from them. Such information is expected to
Integrin-mediated cell adhesion stimulates a cascade of signaling pathways that control cell proliferation, migration, and survival, mostly through tyrosine phosphorylation of signaling molecules. p130Cas, originally identified as a major substrate of v-Src, is a scaffold molecule that interacts with several proteins and mediates multiple cellular events after cell adhesion and mitogen treatment. Here, we describe a novel p130Cas-associated protein named p140Cap (Cas-associated protein) as a new tyrosine phosphorylated molecule involved in integrin- and epidermal growth factor (EGF)-dependent signaling. By affinity chromatography of human ECV304 cell extracts on a MBP-p130Cas column followed by mass spectrometry matrix-assisted laser desorption ionization/time of flight analysis, we identified p140Cap as a protein migrating at 140 kDa. We detected its expression in human, mouse, and rat cells and in different mouse tissues. Endogenous and transfected p140Cap proteins coimmunoprecipitate with ...
The insulin-like growth factor-1 receptor (IGF-1R) plays an important role in transformation and proliferation of malignant cells (1, 2, 3, 4) . The IGF-1R is also important for preventing apoptosis and maintaining the malignant phenotype of tumor cells, and is involved in tumor cell protection against antitumor therapy (1 , 2 , 5) . In contrast, the IGF-1R is not an absolute requirement for normal cell growth (5 , 6) .. The IGF-1R consists of two identical extracellular α-subunits that are responsible for ligand binding, and two identical β-subunits with a transmembrane domain, an intracellular tyrosine kinase, and COOH-terminal domain (7) . The ligand-receptor interaction results in phosphorylation of tyrosine residues in the tyrosine kinase domain (spanning from amino acid 973 to 1229) of the β-subunit. The primary and key sites are the clustered tyrosines at positions 1131, 1135, and 1136 in the activation loop (6 , 8) . Phosphorylation of these tyrosine residues is necessary for ...
Abstract Objective: The bioactive compounds of Rhizopora mucornata were docked against the bacterial enzyme protein tyrosine phosphatase to determine the potential inhibition. In this research the molecular docking analysis of drug compounds with virulent protein was studied. Material and Methods: Protein Tyrosine phosphatase is an enzyme that is being present in staphylococcus infection that plays an important role in cellular localization, enzyme stability. The target enzyme for Staphylococcus aureus was studied and retrieved from PDB. The bioactive compounds from the leaf extract of Rhizopora mucornata was screened for Lipinski rule of Five and ADMET properties. Autodock 4.2.3 software was used for molecular docking, and the visualization was done by using discovery studio 3.1. Result: The compound 3-methyl-2-(2-oxopropyl) furan shows better binding energy with -1.14 Kcal/mol against the enzyme protein tyrosine phosphatase followed by 3-cyclopentylpropionic acid, 4-methoxyphenyl ester +35.14 ...
Looking for tyrosine hydroxylase? Find out information about tyrosine hydroxylase. A specialized enzyme located only in catecholamine-containing nerve cells, where it serves as the primary regulatory or rate-limiting step in catecholamine... Explanation of tyrosine hydroxylase
In our first post on ADHD and tyrosine supplementation, we went through the overview of this pathway. In our last posting, we went through the first step of the process: the conversion of tyrosine (also referred to as L-tyrosine) to DOPA (also referred to as L-DOPA, Levodopa and a number of trade names such as Dopar, Laradopar or Sinemet), and the enzymes and nutrient co-factors involved in this conversion process. L-DOPA is a common treatment method for patients with Parkinsons Disease. I was going to start with the next step of the process today: the conversion of L-DOPA to dopamine, and the major enzymes involved. However, one of our readers from the previous posting on the conversion of Tyrosine to L-DOPA, posed an excellent question on a topic I failed to address (which may be on the minds of several readers). As a result, I will dedicate the remainder of this post to this question and save the next step of the tyrosine to dopamine pathway for the next blog entry. LynneC asked about the ...
Serine/threonine/tyrosine phosphorylation[edit]. Addition of a negatively charged phosphate group can lead to major changes in ...
Retrieved from "https://en.wikipedia.org/w/index.php?title=Talk:Tubulin-tyrosine_ligase&oldid=420266952" ...
Tyrosine kinase inhibitors[edit]. Crystal structure of Abl kinase domain (blue) in complex with 2nd generation tyrosine kinase ... The ABL tyrosine kinase activity of BCR-Abl is elevated relative to wild-type ABL.[11] Since ABL activates a number of cell ... Tyrosine kinase inhibitors specific to such domains as CC, Y177, and Rho (such as imatinib and sunitinib) are important drugs ... The activity of tyrosine kinases is typically regulated in an auto-inhibitory fashion, but the BCR-Abl fusion gene codes for a ...
Erythrose 4-phosphate and phosphoenolpyruvate: phenylalanine, tyrosine, and tryptophan[edit]. Phenylalanine, tyrosine, and ... Tyrosine can also be inhibited at the transcriptional level by the TyrR repressor. TyrR binds to the TyrR boxes on the operon ... In addition, the amino acids arginine, cysteine, glycine, glutamine, histidine, proline, serine, and tyrosine are considered ... Tyrosine is synthesized by the hydroxylation of phenylalanine, an essential amino acid. The pathways for the biosynthesis of ...
Tyrosine. 0.796 g. Valine. 1.199 g. Arginine. 1.545 g. Histidine. 0.726 g. ...
Tyrosine. 0.454 g. Valine. 0.730 g. Arginine. 2.086 g. Histidine. 0.389 g. ...
Tyrosine. 0.452 g. Valine. 0.817 g. Arginine. 2.446 g. Histidine. 0.557 g. ...
Tyrosine. 0.381 g. Valine. 0.701 g. Arginine. 1.516 g. Histidine. 0.255 g. ...
Tyrosine. 1.263 g. Valine. 1.777 g. Arginine. 4.550 g. Histidine. 0.969 g. ...
Tyrosine*. 5.369 g. 2.267 g 3.745 g. 3.409 g. 3.677 g. 2.658 g. 3.675 g. 4.496 g. 2.8 g. 2.500 g. N/A. 4.193 g ...
Tyrosine. 0.513 g. Valine. 0.767 g. Arginine. 0.755 g. Histidine. 0.298 g. ...
Tyrosine. 2.584 g. Valine. 3.512 g. Arginine. 4.147 g. Histidine. 1.085 g. ...
Acetophenones, Tyrosine derivatives, Phenylacetic acids 3-Acetyl-6-methoxybenzaldehyde, Tyrosol, p-Hydroxyphenylacetic acid, ...
Tyrosine. 0.067 g. Valine. 0.135 g. Arginine. 0.173 g. Histidine. 0.067 g. ...
Tyrosine. 0.678 g. Valine. 0.949 g. Arginine. 1.099 g. Histidine. 0.416 g. ...
Tyrosine. 0.103 g. Valine. 0.202 g. Arginine. 0.546 g. Histidine. 0.077 g. ...
Tyrosine. 0.329 g. Valine. 0.679 g. Arginine. 1.060 g. Histidine. 0.389 g. ...
Tyrosine Tyr Y MT-TY 5,826-5,891 H Valine Val V MT-TV 1,602-1,670 L ...
In competitive inhibition, an inhibitor that resembles the normal substrate binds to the enzyme, usually at the active site, and prevents the substrate from binding.[8] At any given moment, the enzyme may be bound to the inhibitor, the substrate, or neither, but it cannot bind both at the same time. During competitive inhibition, the inhibitor and substrate compete for the active site. The active site is a region on an enzyme which a particular protein or substrate can bind to. The active site will only allow one of the two complexes to bind to the site therefore either allowing for a reaction to occur or yielding it. In competitive inhibition the inhibitor resembles the substrate therefore taking its place and binding to the active site of an enzyme. Increasing the substrate concentration would diminish the "competition" for the substrate to properly bind to the active site and allow a reaction to occur.[3] When the substrate is of higher concentration than that of the competitive inhibitor, it ...
Two enzymes convert L-amino acids to D-amino acids. D-Amino-acid racemase, a PLP-dependent enzyme, racemizes amino acids via the formation of the alpha-iminoacids, where the stereogenic center is lost. L-amino-acid oxidases convert L-amino acids to the alpha-ketoacids, which are susceptible to reductive amination. Some amino acids are prone to racemization, one example being lysine, which racemizes via formation pipecolic acid. In peptides, L-amino acid residues slowly racemize, resulting in the formation of some D-amino acid residues. Racemization occurs via deprotonation of the methyne that is alpha to the amido group. Rates increase with pH. Many D-amino acids found in higher organisms are derived from microbial sources. The D-alanine in peptidoglycans that comprise bacterial cell walls helps its host resist attack by proteolytic enzymes. Several antibiotics, e.g. bacitracin, contain D-amino acid residues.[1] ...
Their hydrophobic tendency was equivalent to that of known nonpolar amino acids such as methionine and tyrosine (tyrosine is ...
The COX-2 enzyme was discovered in 1988 by Daniel Simmons, a Brigham Young University researcher.[23] The mouse COX-2 gene was cloned by UCLA scientist Dr. Harvey Herschman, a finding published in 1991.[24]. The basic research leading to the discovery of COX-2 inhibitors has been the subject of at least two lawsuits. Brigham Young University has sued Pfizer, alleging breach of contract from relations BYU had with the company at the time of Dr. Simmons's work.[25][26] A settlement was reached in April 2012 in which Pfizer agreed to pay $450 million.[27][28] The other litigation is based on United States Pat. No. 6,048,850[29] owned by University of Rochester, which claimed a method to treat pain without causing gastro-intestinal distress by selectively inhibiting COX-2. When the patent issued, the university sued Searle (later Pfizer) in a case called, University of Rochester v. G.D. Searle & Co., 358 F.3d 916 (Fed. Cir. 2004). The court ruled in favor of Searle in 2004, holding in essence that ...
... (symbol Gly or G;[5] /ˈɡlaɪsiːn/)[6] is an amino acid that has a single hydrogen atom as its side chain. It is the simplest amino acid (since carbamic acid is unstable), with the chemical formula NH2‐CH2‐COOH. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (GGU, GGC, GGA, GGG). Glycine is integral to the formation of alpha-helices in secondary protein structure due to its compact form. For the same reason, it is the most abundant amino acid in collagen triple-helices. Glycine is also an inhibitory neurotransmitter - interference with its release within the spinal cord (such as during a Clostridium tetani infection) can cause spastic paralysis due to uninhibited muscle contraction. Glycine is a colorless, sweet-tasting crystalline solid. It is the only achiral proteinogenic amino acid. It can fit into hydrophilic or hydrophobic environments, due to its minimal side chain of only one hydrogen atom. The acyl radical is glycyl. ...
A 2017 population-based, matched-cohort study of 93,197 men aged 66 years and older with BPH found that finasteride and dutasteride were associated with a significantly increased risk of depression (HR, 1.94; 95% CI, 1.73-2.16) and self-harm (HR, 1.88; 95% CI, 1.34-2.64) during the first 18 months of treatment, but were not associated with an increased risk of suicide (HR, 0.88; 95% CI, 0.53-1.45).[31][32][33][21] After the initial 18 months of therapy, the risk of self-harm was no longer heightened, whereas the elevation in risk of depression lessened but remained marginally increased (HR, 1.22; 95% CI, 1.08-1.37).[31][32][21] The absolute increase in the rate of depression was 247 per 100,000 patient-years and of self-harm was 17 per 100,000 patient-years.[21][34] As such, on the basis of these findings, it has been stated that cases of depression in patients that are attributable to 5-ARIs will be encountered on occasion, while cases of self-harm attributable to 5-ARIs will be encountered ...
valine, isoleucine, methionine, tyrosine, and phenylalanine. Contents. *1 Structure. *2 Binding to ribonucleases ...
Beyond being a catalyst in the rate-limiting step in testosterone reduction, 5α-reductase isoforms I and II reduce progesterone to 5α-dihydroprogesterone (5α-DHP) and deoxycorticosterone to dihydrodeoxycorticosterone (DHDOC). In vitro and animal models suggest subsequent 3α-reduction of DHT, 5α-DHP and DHDOC lead to neurosteroid metabolites with effect on cerebral function. These neurosteroids, which include allopregnanolone, tetrahydrodeoxycorticosterone (THDOC), and 3α-androstanediol, act as potent positive allosteric modulators of GABAA receptors, and have antidepressant, anxiolytic, prosexual, and anticonvulsant effects.[33] 5α-Dihydrocortisol is present in the aqueous humor of the eye, is synthesized in the lens, and might help make the aqueous humor itself.[34] 5α-Dihydroaldosterone is a potent antinatriuretic agent, although different from aldosterone. Its formation in the kidney is enhanced by restriction of dietary salt, suggesting it may help retain sodium.[35] 5α-DHP is a ...
When both imidazole ring nitrogens are protonated, their 15N chemical shifts are similar (about 200 ppm, relative to nitric acid on the sigma scale, on which increased shielding corresponds to increased chemical shift). NMR shows that the chemical shift of N1-H drops slightly, whereas the chemical shift of N3-H drops considerably (about 190 vs. 145 ppm). This indicates that the N1-H tautomer is preferred, it is presumed due to hydrogen bonding to the neighboring ammonium. The shielding at N3 is substantially reduced due to the second-order paramagnetic effect, which involves a symmetry-allowed interaction between the nitrogen lone pair and the excited π* states of the aromatic ring. As the pH rises above 9, the chemical shifts of N1 and N3 become approximately 185 and 170 ppm. An entirely deprotonated form of the imidazole ring, the imidazolate ion, would be formed only above a pH of 14, and is therefore not physiologically relevant. This change in chemical shifts can be explained by the ...
An amino acid neurotransmitter is an amino acid which is able to transmit a nerve message across a synapse. Neurotransmitters (chemicals) are packaged into vesicles that cluster beneath the axon terminal membrane on the presynaptic side of a synapse in a process called endocytosis.[1]. Amino acid neurotransmitter release (exocytosis) is dependent upon calcium Ca2+ and is a presynaptic response. There are inhibitory amino acids (IAA) or excitatory amino acids (EAA). Some EAA are L-Glutamate, L-Aspartate, L-Cysteine, and L-Homocysteine.[2] These neurotransmitter systems will activate post-synaptic cells.[3] Some IAA include GABA, Glycine, β-Alanine, and Taurine.[2] The IAA depress the activity of post-synaptic cells.[3]. ...
While most amino acids are oxidized in the liver, BCAAs are primarily oxidized in the skeletal muscle and other peripheral tissues.[4] The effects of BCAA administration on muscle growth in rat diaphragm was tested, and concluded that not only does a mixture of BCAAs alone have the same effect on growth as a complete mixture of amino acids, but an amino acid mixture with all but BCAAs has no effect on rat diaphragm muscle growth.[16] Administration of either isoleucine or valine alone had no effect on muscle growth, although administration of leucine alone appears to be nearly as effective as the complete mixture of BCAAs. Leucine indirectly activates p70 S6 kinase as well as stimulates assembly of the eIF4F complex, which are essential for mRNA binding in translational initiation.[16] P70 S6 kinase is part of the mammalian target of rapamycin complex (mTOR) signaling pathway, and has been shown to allow adaptive hypertrophy and recovery of rat muscle.[17] At rest protein infusion stimulates ...
The role of cholesterol in the development of cardiovascular disease was elucidated in the second half of the 20th century.[138] This lipid hypothesis prompted attempts to reduce cardiovascular disease burden by lowering cholesterol. Treatment consisted mainly of dietary measures, such as a low-fat diet, and poorly tolerated medicines, such as clofibrate, cholestyramine, and nicotinic acid. Cholesterol researcher Daniel Steinberg writes that while the Coronary Primary Prevention Trial of 1984 demonstrated cholesterol lowering could significantly reduce the risk of heart attacks and angina, physicians, including cardiologists, remained largely unconvinced.[139] Scientists in academic settings and the pharmaceutical industry began trying to develop a drug to reduce cholesterol more effectively. There were several potential targets, with 30 steps in the synthesis of cholesterol from acetyl-coenzyme A.[140] In 1971, Akira Endo, a Japanese biochemist working for the pharmaceutical company Sankyo, ...
Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L- ... Tyrosine hydroxylase catalyzes the reaction in which L-tyrosine is hydroxylated in the meta position to obtain L-3,4- ... Tyrosine hydroxylase can be inhibited by the drug α-methyl-para-tyrosine (metirosine). This inhibition can lead to a depletion ... Tyrosine hydroxylase catalyzes conversion of tyrosine to L-DOPA using Fe2+, O2 and BH4 ...
Brutons tyrosine kinase (abbreviated Btk or BTK), also known as tyrosine-protein kinase BTK, is an enzyme that in humans is ... non-membrane spanning protein tyrosine kinase activity. • ATP binding. • protein binding. • protein tyrosine kinase activity. ... Brutons tyrosine kinase was discovered in 1993 and is named for Ogden Bruton, who first described XLA in 1952.[5] ... peptidyl-tyrosine autophosphorylation. • B cell activation. • positive regulation of NF-kappaB transcription factor activity. • ...
L Tyrosine. All MeSH CategoriesChemicals and Drugs CategoryAmino Acids, Peptides, and ProteinsAmino AcidsAmino Acids, Cyclic ... Tyrosine. A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE ... Amino Acids, AromaticTyrosineBetalainsBetacyaninsDihydroxyphenylalanineCysteinyldopaLevodopaMethyldopaDiiodotyrosineMelanins ...
... is enantiomer of D-tyrosine (CHEBI:28479) L-tyrosine (CHEBI:17895) is tautomer of L-tyrosine ... L-tyrosine (CHEBI:17895). L-tyrosin-O4-yl group (CHEBI:32768) is substituent group from L-tyrosine (CHEBI:17895). L-tyrosine ... L-tyrosine (CHEBI:17895) is a proteinogenic amino acid (CHEBI:83813) L-tyrosine (CHEBI:17895) is a tyrosine (CHEBI:18186) L- ... L-tyrosine (CHEBI:17895) has role nutraceutical (CHEBI:50733) L-tyrosine (CHEBI:17895) is a L-α-amino acid (CHEBI:15705) L- ...
Tyrosine hydroxylase (TH) deficiency is a disorder that primarily affects movement, with symptoms that may range from mild to ... Tyrosine hydroxylase helps convert the protein building block (amino acid) tyrosine to a catecholamine called dopamine. . ... Tyrosine hydroxylase (TH) deficiency is a disorder that primarily affects movement, with symptoms that may range from mild to ... Mutations in the TH gene result in reduced activity of the tyrosine hydroxylase enzyme. As a result, the body produces less ...
Signals through Kit receptor tyrosine kinase are essential for development of erythrocytes, melanocytes, germ cells, mast cells ... Signals through Kit receptor tyrosine kinase are essential for development of erythrocytes, melanocytes, germ cells, mast cells ...
1-NA-PP1 (CHEBI:52310) has role tyrosine kinase inhibitor (CHEBI:38637). 1-NM-PP1 (CHEBI:52309) has role tyrosine kinase ... BE-23372M (CHEBI:65473) has role tyrosine kinase inhibitor (CHEBI:38637). biochanin A (CHEBI:17574) has role tyrosine kinase ... bosutinib hydrate (CHEBI:68533) has role tyrosine kinase inhibitor (CHEBI:38637). butein (CHEBI:3237) has role tyrosine kinase ... masitinib (CHEBI:63450) has role tyrosine kinase inhibitor (CHEBI:38637). melemeleone B (CHEBI:66690) has role tyrosine kinase ...
Tyrosine is easily made in the body from phenylalanine and is very important to general metabolism, as it is a direct precursor ... of L-tyrosine can be taken two or three times during the day. Since tyrosine has a more stimulating antidepressant effect, ... L-tyrosine has also been used, usually in a dose of 1-2 grams a day, for low sex drive, Parkinsons disease, and in programs ... Tyrosine is easily made in the body from phenylalanine and is very important to general metabolism, as it is a direct precursor ...
... tyrosine which leads to the production of norepinephrine, epinephrine (adrenaline), and thyroid hormone. The ... ... Tyrosine. Saint Johns wort. A medical explanation of the effects of ecstasy on your body. Sleep cycle strategies. ... The human body also uses l-tyrosine to make serotonin and dopamine, two important neurotransmitters. Some reported effects of ... Natural form of the amino acid "tyrosine" which leads to the production of norepinephrine, epinephrine (adrenaline), and ...
Learn about the usage, dosage, side-effects of Tyrosine. ... Tyrosine is essential to regulating mood, helping prevent ... Tyrosine for Stress. Human and animal research suggests that tyrosine acts as an adaptogen, helping the body adapt to and cope ... Given that tyrosine is involved in making melanin, it has been proposed that tyrosine may be a valuable aid in treating ... How to Take Tyrosine. Tyrosine supplements should be taken at least 30 minutes before meals, divided into three daily doses. ...
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Brands A-Z Solgar L-Tyrosine Categories Supplements Amino Acids L-Tyrosine ... Solgar, L-Tyrosine 1 Results (showing 1 - 1) Visit Manufacturers Website » The Best Supplements and Food for a Cardiovascular ...
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Brands A-Z Country Life L-Tyrosine Categories Supplements Amino Acids L-Tyrosine ... Country Life, L-Tyrosine 1 Results (showing 1 - 1) Visit Manufacturers Website » ...
Elevation of plasma tyrosine after a single oral dose of l-tyrosine. Life Sciences, 25, 265-271. doi: 10.1016/0024-3205(79) ... Deijen, J. B. (2005). Tyrosine. In: Lieberman, Kanarek & Prasad, Nutrition brain and behavior (pp. 363-381).Google Scholar ... 2007). Tyrosine supplementation mitigates memory decrements during cold exposure. Physiology and Behavior, 92(4), 575-582. ... During, M. J., Acworth, I. N., & Wurtman, R. J. (1988). Effects of systemic l-tyrosine on dopamine release from rat corpus ...
Cell signaling by receptor tyrosine kinases.. Lemmon MA1, Schlessinger J.. Author information. 1. Department of Biochemistry ... RTK-mediated tyrosine phosphorylation of PLCγ leads to intramolecular binding of the C-terminal SH2 domain to phosphotyrosine ... On the other hand, H2O2 inhibits protein tyrosine phosphatases (PTPs) and thus, prolongs or increases activity of EGFR by a ... Human receptor tyrosine kinases (RTKs) contain 20 subfamilies, shown here schematically with the family members listed beneath ...
... and methods of using them to treat tyrosine kinase-dependent diseases and conditions in mammals: wherein n is an integer, ... regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, ... Tyrosine kinases can be categorized as receptor type or non-receptor type. Receptor type tyrosine kinases have an extracellular ... For example, the Bcr-Abl tyrosine kinase is the constitutive abnormal tyrosine kinase created by the Philadelphia chromosome ...
Learn more about Tyrosine uses, effectiveness, possible side effects, interactions, dosage, user ratings and products that ... Acétyl-L-Tyrosine, L-Tyrosine, N-Acetyl L-Tyrosine, N-Acetyl-L-Tyrosine, N-Acétyl L-Tyrosine, N-Acetyl-Tyrosine, N-Acétyl- ... As a result they cant make tyrosine. To meet their bodies needs, supplemental tyrosine is given.. Tyrosine is also commonly ... Tyrosine can also be found in dairy products, meats, fish, eggs, nuts, beans, oats, and wheat.. Tyrosine is most commonly used ...
Tyrosine and tumors. By Hunters recollection, he and his colleagues stumbled on tyrosine phosphorylation through their work on ... was also a tyrosine kinase. This led Hunter to generate sequence alignments of the viral tyrosine kinase proteins, as well as ... A legacy of tyrosine. Tony Hunter, the Salk Institute biochemist who discovered this amino acids phosphorylation, was ... Today, 40 tyrosine kinase inhibitors have been approved by the Food and Drug Administration as cancer therapies. ...
Tyrosine kinases,state=autocollapse}}. *shows the template collapsed to the title bar if there is a {{navbar}}. , a {{sidebar}} ... Tyrosine kinases,state=collapsed}}. to show the template collapsed, i.e., hidden apart from its title bar ... Tyrosine kinases,state=expanded}}. to show the template expanded, i.e., fully visible ... Retrieved from "https://en.wikipedia.org/w/index.php?title=Template:Tyrosine_kinases&oldid=737502993" ...
Tyrosine residues may also be modified by the addition of a sulfate group, a process known as tyrosine sulfation.[7] Tyrosine ... namely meta-tyrosine (also known as 3-hydroxyphenylalanine, L-m-tyrosine, and m-tyr) and ortho-tyrosine (o-tyr or 2- ... It transforms L-tyrosine into p-coumaric acid. Precursor to pigmentsEdit. Tyrosine is also the precursor to the pigment melanin ... Ortho- and meta-tyrosineEdit. Enzymatic oxidation of tyrosine by phenylalanine hydroxylase (top) and non-enyzmatic oxidation by ...
p, Some scientific research has been conducted to understand the biological function and importance of tyrosine, a non- ... essential amino acid that, however, plays a pivotal role as a donor of phospho-tyrosine in signal transduction within the cells ... in 1960s and thereafter has uncovered an involvement of tyrosine phosphorylation and dephosphorylation as a key feature in on- ... This book will cover several aspects of biological as well as physicochemical features of tyrosine in all related scientific ...
... and laboratory protocols on the more essential aspects of protein tyrosine phosphatase (PTP) function and regulation, including ... Protein Tyrosine Phosphatases. Book Subtitle. Methods and Protocols. Editors. * Rafael Pulido Series Title. Methods in ... Authoritative and practical, Protein Tyrosine Phosphatases: Methods and Protocols aims to aid researchers in better defining ... Tailor-Made Protein Tyrosine Phosphatases: In Vitro Site-Directed Mutagenesis of PTEN and PTPRZ-B ...
Treatments and Tools for tyrosine. Find tyrosine information, treatments for tyrosine and tyrosine symptoms. ... tyrosine - MedHelps tyrosine Center for Information, Symptoms, Resources, ... I was taking l-tyrosine and 5-htp for some anxiety issues i have.It was working great but t... ... L-Tyrosine and the Thomas Recipe, how much - Addiction: Substance Abuse Community ...
Learn about the potential side effects of tyrosine. Includes common and rare side effects information for consumers and ... Applies to tyrosine: oral capsule, oral powder. Get emergency medical help if you have signs of an allergic reaction: hives; ... Although not all side effects are known, tyrosine is thought to be likely safe in most adults when taken for up to 3 months. ...
APPFORMIN - metformin hydrochloride, tyrosine To receive this label RSS feed. Copy the URL below and paste it into your RSS ... In addition, tyrosine deficiencies have been reported in the medical literature in obese and morbidly obese patients. Thus, ... Products containing L-tyrosine are contraindicated in those with the inborn errors of metabolism alkaptonuria and tyrosinemia ... Products containing tyrosine are also contraindicated in patients taking non-selective monoamine oxidase (MAO) inhibitors. ...
A reactive N=N species generated in the five-membered ring reacts with the C-H bonds adjacent to the tyrosine OH group. ... Alvarez-Dorta et al. show that tyrosine residues on proteins, including insulin and bovine serum albumin, can be targeted by ... For example, for electron-rich tyrosine, click methods have been developed based on cyclic diazodicarboxyamide anchors, but ...
Tyrosine Kinases RT2 Profiler PCR Array The Rat Tyrosine Kinases RT2 Profiler PCR Array profiles the expression of 84 receptor ... Tyrosine Kinases RT2 Profiler PCR Array The Human Tyrosine Kinases RT2 Profiler PCR Array profiles the expression of 84 ... Tyrosine Kinases RT2 Profiler PCR Array The Mouse Tyrosine Kinases RT2 Profiler PCR Array profiles the expression of 84 ... Receptor Tyrosine Kinase (Panel II) qBiomarker Somatic Mutation PCR Array The Human Receptor Tyrosine Kinase (RTK) Pathways ...
We have found that viral pp60src and the endogenous pp60sarc of birds and of mammals catalyze the phosphorylation of a tyrosine ... It has been shown recently that a tyrosine in both the 60,000-dalton tumor antigen of polyoma virus (20) and p120 of Abelson ... We favor the idea that the phosphorylation of tyrosine carried out by pp60src is an end-state protein modification that is ... Phosphorylated tyrosines are rare in uninfected cells and significantly more abundant in cells transformed by RSV. It is ...
  • Kinases that specifically phosphorylate tyrosine residues2. (slideshare.net)
  • Tyrosine kinases can be further subdivided into1. (slideshare.net)
  • Receptor tyrosine kinases eg: EGFR, PDGFR, FGFR2. (slideshare.net)
  • The molecular basis of phospho-tyrosyl-regulation of Src-family and Syk-family protein tyrosine kinases in signaling pathways is a current focus of the lab. (purdue.edu)
  • Cell signaling by receptor tyrosine kinases. (nih.gov)
  • Recent structural studies of receptor tyrosine kinases (RTKs) have revealed unexpected diversity in the mechanisms of their activation by growth factor ligands. (nih.gov)
  • Human receptor tyrosine kinases (RTKs) contain 20 subfamilies, shown here schematically with the family members listed beneath each receptor. (nih.gov)
  • Top: In general, receptor tyrosine kinases (RTKs) associate into dimers when ligand (red) binds to their extracellular regions. (nih.gov)
  • His discovery that the activity of tyrosine kinases drives the growth of cancerous cells ultimately led to the development of tyrosine kinase inhibitors and the groundbreaking leukemia therapy Gleevec, as well as an entire subfield of biochemical regulation. (asbmb.org)
  • According to Hunter, this provided an immediate hint that cells might also have tyrosine kinases. (asbmb.org)
  • This led Hunter to generate sequence alignments of the viral tyrosine kinase proteins, as well as protein kinases that phosphorylate serine and threonine, which revealed that the catalytic domain of tyrosine kinase has a series of conserved short sequence motifs that are essential for transferring phosphate. (asbmb.org)
  • When those genes were combined with analysis of the human genome sequence, the researchers ultimately wound up discovering nearly 500 human kinases, about 90 of which are tyrosine kinases. (asbmb.org)
  • Some of the tyrosine residues can be tagged (at the hydroxyl group) with a phosphate group ( phosphorylated ) by protein kinases . (wikipedia.org)
  • His research interest is the role played by protein-tyrosine kinases in transmembrane signal transduction mechanisms such as in the cancer cells and the fertilized eggs. (intechopen.com)
  • The protein tyrosine kinase superfamily includes roughly 60 receptor tyrosine kinases (RTKs) and about 30 intracellular tyrosine kinases. (qiagen.com)
  • Upon activation, RTKs dimerize and autophosphorylate their intracellular domains, initiating downstream signaling that often includes non-receptor tyrosine kinases. (qiagen.com)
  • Non-receptor tyrosine kinases include a catalytic domain and a regulatory domain, which vary for each family. (qiagen.com)
  • Tyrosine kinases and their downstream signaling pathways are involved in many basic biological processes, such as growth, proliferation, and differentiation. (qiagen.com)
  • These processes are commonly dysregulated during oncogenesis, often due to frequent mutations of key tyrosine kinases or regulators. (qiagen.com)
  • These oncogenic processes make the tyrosine kinase superfamily members attractive drug targets, and there are several chemotherapeutics targeting tyrosine kinases already on the market (e.g., imatinib mesylate). (qiagen.com)
  • The Human Tyrosine Kinases RT 2 Profiler PCR Array profiles the expression of 84 receptor and non-receptor tyrosine kinase genes. (qiagen.com)
  • The recognition motif for phosphorylation by Abl is I/V/L Y XXP/F. Abl, like many cytosolic protein tyrosine kinases, preferentially phosphorylates sites recognized by its own SH2 domain, selects substrates with large hydrophobic amino acids at the +3 position and β-branched amino acids at the -1 position (4). (neb.com)
  • It is now clear that tyrosine kinases represent attractive targets for therapeutic intervention in cancer. (pnas.org)
  • Recent successful development of targeted intervention agents has been based on the use of small molecules and antibodies directed to disregulated tyrosine kinases ( 2 , 3 ). (pnas.org)
  • Tyrosine kinases are a subgroup of the larger class of protein kinases . (bionity.com)
  • There are over 100 3D structures of tyrosine kinases available at the Protein Data Bank . (bionity.com)
  • Most tyrosine kinases have an associated protein tyrosine phosphatase. (bionity.com)
  • Approximately 2000 kinases are known and more than 90 Protein Tyrosine Kinases (PTKs) have been found in the human genome. (bionity.com)
  • At present, 58 receptor tyrosine kinases (RTKs) are known, grouped into 20 subfamilies. (bionity.com)
  • In humans, there are 32 cytoplasmic protein tyrosine kinases ( EC (bionity.com)
  • Most animal cells contain one or more members of the Src family of tyrosine kinases. (bionity.com)
  • A mutation that causes certain tyrosine kinases to be constitutively active has been associated with several cancers. (bionity.com)
  • Imatinib (brand names Gleevec and Glivec) is a drug able to bind the catalytic cleft of these tyrosine kinases, inhibiting its activity. (bionity.com)
  • The development of the so-called "targeted therapies", particularly those drugs that inhibit the activity of tyrosine kinases, has become a remarkable progress in the treatment of neoplastic diseases. (rti.org)
  • Here we summarize what is known up to date about the cardiotoxicity of drugs targeting the tyrosine kinases. (rti.org)
  • Therefore, tyrosine phosphorylation-dependent signaling involving receptor tyrosine kinases, mitogen-activated protein kinases, Abl, Src, and Pyk2 is known to be initiated or amplified by reactive oxidants. (sciencemag.org)
  • Receptor tyrosine kinases are a large family of cell-surface receptors that respond to a variety of intercellular signals, including insulin, growth factors such as epidermal growth factor (EGF) and fibroblast growth factor (FGF), and molecules involved in neuronal guidance. (cshlpress.com)
  • Written and edited by experts in the field, Signaling by Receptor Tyrosine Kinases from Cold Spring Harbor Perspectives in Biology discusses the mechanisms underlying receptor tyrosine kinase signaling, including ligand processing, receptor dimerization, receptor trafficking, and the roles of adapters. (cshlpress.com)
  • However, development of therapeutics targeting the family of protein tyrosine phosphatases has lagged far behind that of kinases. (soci.org)
  • Attempts to normalize aberrant tyrosine phosphorylation levels in disease states currently involve either the application of small compounds that inhibit tyrosine kinases (TKs) or the addition of growth factors or their mimetics to boost receptor-type TK activity. (mdpi.com)
  • Tyrosine kinases are enzymes capable of phosphorylating tyrosine residues within proteins. (novusbio.com)
  • c-Src phosphorylates specific tyrosine residues in other tyrosine kinases. (wikipedia.org)
  • c-Src can be activated by many transmembrane proteins that include: adhesion receptors, receptor tyrosine kinases, G-protein coupled receptors and cytokine receptors. (wikipedia.org)
  • Most studies have looked at the receptor tyrosine kinases and examples of these are platelet derived growth factor receptor (PDGFR) pathway and epidermal growth factor receptor (EGFR). (wikipedia.org)
  • NMR structure of the immunoreceptor tyrosine-based activation motif signaling region of the B cell antigen receptor. (purdue.edu)
  • Signals through Kit receptor tyrosine kinase are essential for development of erythrocytes, melanocytes, germ cells, mast cells and interstitial cells of Cajal (ICCs). (springer.com)
  • Not long afterward, a group led by Stanley Cohen at Vanderbilt University reported that the transmembrane epidermal growth receptor protein, or EGFR, was also a tyrosine kinase. (asbmb.org)
  • The Human Receptor Tyrosine Kinase (RTK) Pathways qBiomarker Somatic Mutation PCR Array is a translational research tool that allows rapid and accurate profiling of the somatic mutation status for. (qiagen.com)
  • Here we report on the sequence analysis of members of the receptor tyrosine kinase (RTK) gene family in the genomes of glioblastoma brain tumors. (pnas.org)
  • To find molecular targets, we have sequenced the coding exons for the kinase domains of 20 human receptor tyrosine kinase (RTK) genes in glioblastomas. (pnas.org)
  • An isolated nucleic acid molecule encoding a novel human receptor type tyrosine kinase gene, KDR, is disclosed. (google.es)
  • The present invention relates to an isolated nucleic acid molecule (polynucleotide) which encodes a human receptor tyrosine kinase, KDR, which is expressed on human endothelial cells. (google.es)
  • An example is PDB 1IRK, the crystal structure of the tyrosine kinase domain of the human insulin receptor . (bionity.com)
  • The first non-receptor tyrosine kinase identified was the v-src oncogenic protein. (bionity.com)
  • The small molecule tyrosine kinase inhibitor (TKI) imatinib has revolutionized the treatment of chronic myeloid leukemia, and trastuzumab, the humanized monoclonal antibody against the ERBB2 receptor tyrosine kinase, has proved to have a high efficacy in 25% of breast cancers. (rti.org)
  • A study published in Science Advances reveals the mechanism by which the receptor tyrosine kinase RET can increase neuronal survival in degenerative diseases. (phys.org)
  • We demonstrated that protein tyrosine phosphatase non-receptor 22 (PTPN22), variants in which are associated with chronic inflammatory disorders, dephosphorylates NLRP3 upon inflammasome induction, allowing efficient NLRP3 activation and subsequent IL-1β release. (jci.org)
  • Among the responsive sites, 20 were previously known to be tyrosine phosphorylated with insulin treatment, including sites on the insulin receptor and insulin receptor substrate-1. (diabetesjournals.org)
  • Insulin binds to the insulin receptor at the cell surface and activates its tyrosine kinase activity, leading to autophosphorylation and phosphorylation of several receptor substrates. (diabetesjournals.org)
  • Phosphorylation of selected tyrosine sites on receptor substrates is known to activate different pathways leading to increased glucose uptake, lipogenesis, and glycogen and protein synthesis, as well as to stimulation of cell growth ( 1 , 2 ). (diabetesjournals.org)
  • For instance, serine phosphorylation on insulin receptor substrate (IRS)-1 induced by a variety of factors has been shown to interfere with the activating effects of tyrosine phosphorylation by decreasing binding to the insulin receptor or increasing degradation of IRS-1 ( 1 , 3 , 4 ). (diabetesjournals.org)
  • Ser/Thr phosphorylation of the insulin receptor has also been shown to decrease tyrosine kinase activity ( 1 ). (diabetesjournals.org)
  • Many of these factors are reflected in decreased amounts of the tyrosine-phosphorylated receptor and receptor substrates with concomitant reduction in downstream signaling. (diabetesjournals.org)
  • Even though tyrosine phosphorylation plays a key role in insulin signaling, rather limited knowledge of specific phosphorylation sites, mainly focusing on tyrosine phosphorylation on the insulin receptor and IRS-1, is available so far. (diabetesjournals.org)
  • Targeting Receptor-Type Protein Tyrosine Phosphatases with Biotherapeutics: Is Outside-in Better than Inside-Out? (mdpi.com)
  • pronounced "sarc", as it is short for sarcoma), is a non-receptor tyrosine kinase protein that in humans is encoded by the SRC gene. (wikipedia.org)
  • Tyrosine residues may also be modified by the addition of a sulfate group, a process known as tyrosine sulfation . (wikipedia.org)
  • For example, for electron-rich tyrosine, click methods have been developed based on cyclic diazodicarboxyamide anchors, but activation with chemical oxidants can also modify lysine residues or create products with limited aqueous stability. (sciencemag.org)
  • show that tyrosine residues on proteins, including insulin and bovine serum albumin, can be targeted by electrochemically oxidizing phenyl urazoles without affecting amine or thiol groups of other amino acids. (sciencemag.org)
  • Catalyzes the O-sulfation of tyrosine residues within acidic motifs of polypeptides, using 3'-phosphoadenylyl sulfate (PAPS) as cosubstrate. (uniprot.org)
  • Sulfation sites are have a tyrosine residues exposed on the surface of the protein typically surrounded by acidic residues, a detailed description of the characteristics of the sulfation site is available from PROSITE (PROSITE pattern: PS00003)[1]. (bionity.com)
  • A major mechanism of injury associated with the production of nitric oxide (NO*) in vivo is due to its diffusion-limited reaction with superoxide to form peroxynitrite, which in turn may cause nitration of protein tyrosine residues. (nih.gov)
  • It is a truncated form of the human T-Cell protein tyrosine phosphatase (residues 1-317) which lacks a C-terminal regulatory domain (1,2). (neb.com)
  • Protein phosphatase exclusively specific to phospho-tyrosine residues in proteins. (neb.com)
  • TC PTP can be used to release phosphate groups specifically from phospho-tyrosine residues in proteins. (neb.com)
  • We are also actively investigating the regulation of Syk tyrosine kinase binding to membrane immune receptors and other signaling proteins. (purdue.edu)
  • Tyrosine (symbol Tyr or Y ) [1] or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins . (wikipedia.org)
  • We infer from these observations that pp60 src is a novel protein kinase and that the modification of proteins via the phosphorylation of tyrosine is essential to the malignant transformation of cells by Rous sarcoma virus. (pnas.org)
  • This is additional evidence of the functional similarity of these structurally related proteins and demonstrates that all uninfected vertebrate cells contain at least one protein kinase that phosphorylates tyrosine. (pnas.org)
  • Types of human proteins known to undergo tyrosine sulfation include adhesion molecules, G-protein-coupled receptors, coagulation factors, serine protease inhibitors , extracellular matrix proteins, and hormones. (bionity.com)
  • Detection and purification of tyrosine-sulfated proteins using a novel anti-sulfotyrosine monoclonal antibody. (bionity.com)
  • To assess the physiological role of tyrosine nitration, it is crucial to identify the proteins that become nitrated. (nih.gov)
  • Therefore, we treated lysates from RAW 264.7 cells with 1 mM peroxynitrite and immunoprecipitated tyrosine nitrated proteins. (nih.gov)
  • Tyrosine is an amino acid found in meat proteins. (memorialhealth.com)
  • Ligand binding stimulates the tyrosine kinase activity of the receptors, leading to recruitment of enzymes and adapter proteins that activate intracellular signaling pathways that control cell proliferation, differentiation, and numerous other biological processes. (cshlpress.com)
  • It has resulted in the identification and relative temporal quantification of 122 tyrosine phosphorylation sites on 89 proteins. (diabetesjournals.org)
  • These results show that insulin-elicited tyrosine phosphorylation is extensive and implicate a number of hitherto unrecognized proteins in insulin action. (diabetesjournals.org)
  • We have recently developed a mass spectrometric methodology for the identification and quantification of tyrosine phosphorylation sites on many proteins ( 5 ). (diabetesjournals.org)
  • Tyrosine is a conditionally essential amino acid derived from the essential amino acid phenylalanine which the body uses to synthesize proteins. (ei-resource.org)
  • Tyrosine hydroxylase or tyrosine 3-monooxygenase is the enzyme responsible for catalyzing the conversion of the amino acid L -tyrosine to L -3,4-dihydroxyphenylalanine ( L -DOPA). (wikipedia.org)
  • Tyrosine hydroxylase catalyzes the rate limiting step in this synthesis of catecholamines . (wikipedia.org)
  • In humans, tyrosine hydroxylase is encoded by the TH gene , [6] and the enzyme is present in the central nervous system (CNS), peripheral sympathetic neurons and the adrenal medulla . (wikipedia.org)
  • [6] Tyrosine hydroxylase, phenylalanine hydroxylase and tryptophan hydroxylase together make up the family of aromatic amino acid hydroxylases (AAAHs). (wikipedia.org)
  • Tyrosine hydroxylase catalyzes the reaction in which L -tyrosine is hydroxylated in the meta position to obtain L -3,4-dihydroxyphenylalanine ( L -DOPA). (wikipedia.org)
  • Like the other aromatic amino acid hydroxylases (AAAHs), tyrosine hydroxylase use the cofactor tetrahydrobiopterin (BH 4 ) under normal conditions, although other similar molecules may also work as a cofactor for tyrosine hydroxylase. (wikipedia.org)
  • [8] Each of the four subunits in tyrosine hydroxylase is coordinated with an iron (II) atom presented in the active site. (wikipedia.org)
  • [11] Since L -DOPA is the precursor for the neurotransmitters dopamine, noradrenaline and adrenaline, tyrosine hydroxylase is therefore found in the cytosol of all cells containing these catecholamines . (wikipedia.org)
  • This initial reaction catalyzed by tyrosine hydroxylase has been shown to be the rate limiting step in the production of catecholamines. (wikipedia.org)
  • Tryptophan is a poor substrate for tyrosine hydroxylase, however it can hydroxylate L -phenylalanine to form L -tyrosine and small amounts of 3-hydroxyphenylalanine. (wikipedia.org)
  • Tyrosine hydroxylase may also be involved in other reactions as well, such as oxidizing L -DOPA to form 5-S-cysteinyl-DOPA or other L -DOPA derivatives. (wikipedia.org)
  • Tyrosine hydroxylase from rat showing two of its domains , the tetramerization domain (pink) and the catalytic domain (blue). (wikipedia.org)
  • Tyrosine hydroxylase is a tetramer of four identical subunits ( homotetramer ). (wikipedia.org)
  • Tyrosine hydroxylase (TH) deficiency is a disorder that primarily affects movement, with symptoms that may range from mild to severe. (medlineplus.gov)
  • The TH gene provides instructions for making the enzyme tyrosine hydroxylase, which is important for normal functioning of the nervous system. (medlineplus.gov)
  • Tyrosine hydroxylase takes part in the pathway that produces a group of chemical messengers (hormones) called catecholamines. (medlineplus.gov)
  • Tyrosine hydroxylase helps convert the protein building block (amino acid) tyrosine to a catecholamine called dopamine . (medlineplus.gov)
  • Mutations in the TH gene result in reduced activity of the tyrosine hydroxylase enzyme. (medlineplus.gov)
  • Furukawa Y, Kish S. Tyrosine Hydroxylase Deficiency. (medlineplus.gov)
  • Furukawa Y, Kish SJ, Fahn S. Dopa-responsive dystonia due to mild tyrosine hydroxylase deficiency. (medlineplus.gov)
  • In dopaminergic cells in the brain, tyrosine is converted to L-DOPA by the enzyme tyrosine hydroxylase (TH). (wikipedia.org)
  • Tyrosine Hydroxylase (phospho-Ser19) antibody detects endogenous levels of Tyrosine Hydroxylase only when phosphorylated at serine19. (abcam.com)
  • Four Isoforms of Tyrosine Hydroxylase are Expressed in Human Brain. (abcam.com)
  • Tyrosine Hydroxylase Activity in Parkinson's Disease. (rainbow.coop)
  • Tyrosine hydroxylase is a BH4 (tetrahydrobiopterin) dependent enzyme which increases the conversion of tyrosine, an amino acid, to l-DOPA (l-dihydroxyphenylalanine. (rainbow.coop)
  • BCR-ABL Tyrosine Kinase Inhibitors eg: Imatinib Mesylate, Dasatinib, and Nilotinib.2. (slideshare.net)
  • S B Bhise, Abhijit D. Nalawade and Hitesh Wadhawa, Role of protein tyrosine kinase inhibitors in cancer therapeutics . (bionity.com)
  • A new business intelligence report released by Up Market Research with title "Global Tyrosine Kinase Inhibitors Market Research Report 2019" that targets and provides comprehensive market analysis with future prospects to 2026. (openpr.com)
  • Tyrosine Kinase Inhibitors Market research report delivers a close watch on leading competitors with strategic analysis, micro and macro market trend and scenarios, pricing analysis and a holistic overview of the market situations in the forecast period. (openpr.com)
  • The report contains basic, secondary and advanced information pertaining to the Tyrosine Kinase Inhibitors Market global status and trend, market size, share, growth, trends analysis, segment and forecasts from 2019 - 2026. (openpr.com)
  • The report for Tyrosine Kinase Inhibitors Market analysis & forecast 2019- 2026 is segmented into Product Segment, Application Segment & Major players. (openpr.com)
  • Tyrosine Kinase Inhibitors Market Analysis and Forecast 2019- 2026" report helps the clients to take business decisions and to understand strategies of major players in the industry. (openpr.com)
  • What is the role of tyrosine kinase inhibitors in the etiology of macrocytosis? (medscape.com)
  • The tyrosine kinase inhibitors sunitinib and imatinib have been shown to induce macrocytosis in patients with a variety of cancers, including renal cell carcinomas (RCCs), gastrointestinal stromal tumors (GISTs), and breast cancer. (medscape.com)
  • People taking MAO inhibitors that have been prescribed for depression need to strictly limit their intake of foods containing Tyrosine, and should not take any supplements containing this amino acid as it can lead to a sudden increase in blood pressure. (herbalremedies.com)
  • Hendriks W, Bourgonje A, Leenders W, Pulido R. Proteinaceous Regulators and Inhibitors of Protein Tyrosine Phosphatases. (mdpi.com)
  • A tyrosine residue also plays an important role in photosynthesis . (wikipedia.org)
  • Tyrosine sulfation is a posttranslational modification where a sulfate group is added to a tyrosine residue of a protein molecule. (bionity.com)
  • The reaction catalyzed by TPST is a transfer of sulfate from the universal sulfate donor 3'-phosphoadenosine 5'-phosphosulfate (PAPS) to the side-chain hydroxyl group of a tyrosine residue. (bionity.com)
  • A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to a tyrosine residue in a protein . (bionity.com)
  • Because protein tyrosine phosphatases (PTPs) all harbor an absolutely conserved catalytic cysteine residue, oxidation of this residue inactivates PTPs, rendering tyrosine kinase signaling pathways highly sensitive to the local redox environment. (sciencemag.org)
  • Each side of the dimer protein includes pyridoxal phosphate (PLP) bonded to the Lys280 residue of the tyrosine aminotransferase molecule. (wikipedia.org)
  • This induces long-range allostery via protein domain dynamics, causing the structure to be destabilized, resulting in the opening up of the SH3, SH2 and kinase domains and the autophosphorylation of the residue tyrosine 416. (wikipedia.org)
  • Tyrosine is easily made in the body from phenylalanine and is very important to general metabolism, as it is a direct precursor of both adrenaline (as well as norepinephrine and dopamine) and thyroid hormones, all stimulants to metabolism and the nervous system. (healthy.net)
  • The human body also uses l-tyrosine to make serotonin and dopamine , two important neurotransmitter s. (everything2.com)
  • As a building block for several important brain chemicals, tyrosine is needed to make epinephrine, norepinephrine, serotonin, and dopamine, all of which work to regulate mood. (healthyplace.com)
  • Finally, in the mid 1980s some researchers speculated that tyrosine may be useful for treating Parkinson's because this amino acid can increase dopamine levels. (healthyplace.com)
  • In this study, we investigated whether creativity in convergent- and divergent-thinking tasks is promoted by the food supplement l -Tyrosine (TYR)-a biochemical precursor of dopamine, which is assumed to drive cognitive control and creativity. (springer.com)
  • Tyrosine influences pigment production and the development of dopamine in the brain. (healthline.com)
  • Take tyrosine for instance, your body uses this amino acid to produce epinephrine, norepinephrine, and dopamine, brain chemicals that influence mood. (livestrong.com)
  • Besides being necessary for normal growth and development, tyrosine serves as a precursor to the neurotransmitters dopamine, norepinephrine and epinephrine. (ralphs.com)
  • Tyrosine improves clinical signs of dopamine-dependent depression. (greenmedinfo.com)
  • Tyrosine is a precursor of adrenaline and the neurotransmitters norepinephrine and dopamine, which stimulates metabolism and the nervous system, and regulates mood. (herbalremedies.com)
  • L-Tyrosine, a constituent of dietary protein, is a substrate or precursor to the catecholamine neurotransmitters norepinephrine, epinephrine and dopamine, the levels of which can be affected by the amount of tyrosine consumed. (jarrow.com)
  • N-Acetyl Tyrosine supports brain function by improving the synthesis of the catecholamines norepinephrine and dopamine (neurotransmitters). (patientslikeme.com)
  • NOW L-Tyrosine is a non-essential amino acid that plays an important role in the production of neurotransmitters dopamine and norepinephrine. (netrition.com)
  • dopamine from L-tyrosine: step 1/2. (abcam.com)
  • Production of Catecholamines - Tyrosine is the basic building block of this important group of neurotransmitters which include dopamine, adrenaline/epinephrine, and noradrenaline/norepinephrine have an energizing effect on the brain. (ei-resource.org)
  • Since tyrosine is the amino acid building block of the energizing catecholamine neurotransmitters such as dopamine and noradrenaline/norepinephrine I thought it would be well worth trying it to see if it alleviated my symptoms. (ei-resource.org)
  • This quality free-form amino acid supplement supplies 500 mg of L-tyrosine which is a precursor to the neurotransmitter dopamine, as well as to the adrenal hormones norepinephrine and epinephrine which may help to heighten mental alertness, offset physical and mental fatigue. (prosource.net)
  • N-Acetyl Tyrosine supports brain function by supporting the synthesis of the catecholamines norepinephrine and dopamine (neurotransmitters). (jarrow.com)
  • The present invention relates to compounds of the Formula I, the pharmaceutically acceptable salts and stereoisomers thereof, which inhibit, regulate and/or modulate tyrosine kinase signal transduction, compositions which contain these compounds, and methods of using them to treat tyrosine kinase-dependent. (google.com)
  • Tyrosine phosphorylation is considered to be one of the key steps in signal transduction and regulation of enzymatic activity. (wikipedia.org)
  • Some scientific research has been conducted to understand the biological function and importance of tyrosine, a non-essential amino acid that, however, plays a pivotal role as a donor of phospho-tyrosine in signal transduction within the cells. (intechopen.com)
  • QIAGEN provides a broad range of assay technologies for tyrosine kinase research that enable analysis of gene expression and regulation, epigenetic modification, and signal transduction pathway activation. (qiagen.com)
  • Protein tyrosine phosphatase-1B (PTP-1B) negatively regulates the signaling pathways of insulin and leptin, two hormones involved in the central regulation of energy balance ( 1 ). (diabetesjournals.org)
  • We describe a nonradioisotopic method that discriminates between reduced and oxidatively modified tyrosine phosphatases, thus facilitating studies that may mechanistically link oxidant activity with specific signaling pathways. (sciencemag.org)
  • In addition to activation of these pathways by tyrosine phosphorylation, several mechanisms of downregulating the response to insulin stimulation have also been identified. (diabetesjournals.org)
  • The family of protein tyrosine phosphatases (PTPs) play critical roles in celluar signalling pathways and are recognised as potential drug targets in diabetes, cancer and cardiovascular disease. (soci.org)
  • I switched to Acetyl L-Tyrosine which has the same benefits but better pharmacological properties. (patientslikeme.com)
  • I switched from taking L-Tyrosine to taking Acetyl L-Tyrosine because of better absorption and delivery of the Tyrosine across the blood brain barrier. (patientslikeme.com)
  • After a few other experiences with supplements that supply nutrients in a form closer to the end products used by the body I decided to give the N-acetyl-L-Tyrosine form a try. (ei-resource.org)
  • The positive effects on my mood and mental functioning I get with N-acetyl-L-Tyrosine last for around 3-4 hours so I need to take more than one dose per day to maintain them. (ei-resource.org)
  • Tyrosine is an important precursor for neurotransmitters in the body. (aminoz.com.au)
  • Tyrosine is also the precursor to the pigment melanin. (wikipedia.org)
  • Tyrosine (or its precursor phenylalanine) is needed to synthesize the benzoquinone structure which forms part of coenzyme Q10. (wikipedia.org)
  • Bruton's tyrosine kinase (abbreviated Btk or BTK ), also known as tyrosine-protein kinase BTK , is an enzyme that in humans is encoded by the BTK gene . (wikipedia.org)
  • L-tyrosine + 2-oxoglutarate ⇌ {\displaystyle \rightleftharpoons } 4-hydroxyphenylpyruvate + L-glutamate In humans, the tyrosine aminotransferase protein is encoded by the TAT gene. (wikipedia.org)
  • Natural form of the amino acid " tyrosine " which leads to the production of norepinephrine , epinephrine ( adrenaline ), and thyroid hormone . (everything2.com)
  • Aside from being a proteinogenic amino acid , tyrosine has a special role by virtue of the phenol functionality. (wikipedia.org)
  • Scientists have been searching for it for decades: the enzyme that cuts the amino acid tyrosine off an important part of the cell's skeleton. (phys.org)
  • The amino acid tyrosine is superior to synthetic T4/T3 combination in reducing TSH and improving mood in winter, whereas the T4/T3 combination worsens mood in the summer with no improvement in winter. (greenmedinfo.com)
  • Structures of the three main molecules involved in chemical reaction catalyzed by the tyrosine aminotransferase enzyme are shown below: the amino acid tyrosine, the prosthetic group pyridoxal phosphate, and the resulting product 4-hydroxyphenylpyruvate. (wikipedia.org)
  • If I use 60mg of Armor thyroid per day, can I also use Tyrosine supplements of 500mg/3xday? (hubpages.com)
  • This does not mean, however, that taking tyrosine supplements will avoid these particular circumstances. (healthyplace.com)
  • Because tyrosine stimulates the production of serotonin, some experts speculate that L-tyrosine supplements may improve serotonin levels and decrease PMS symptoms. (healthyplace.com)
  • Tyrosine is most commonly used in protein supplements to treat an inherited disorder called phenylketonuria (PKU). (webmd.com)
  • Will L-Tyrosine Supplements Help My Erectile Dysfunction? (healthline.com)
  • In the search for treatment options, L-tyrosine supplements are increasingly suggested to those with ED. Some research paints an optimistic picture, but how reliable is L-tyrosine? (healthline.com)
  • Aside from high protein foods and ED supplements, it's also common to find tyrosine in other health supplements. (healthline.com)
  • Before you take any tyrosine supplements, be sure to let your doctor know. (healthline.com)
  • If you begin to experience side effects you didn't have prior to starting L-tyrosine, stop taking the supplements and contact your doctor immediately. (healthline.com)
  • As of now, there don't appear to be too many major side effects associated with tyrosine supplements. (healthline.com)
  • Although you can take supplements of tyrosine, it is recommended to meet the needs of this amino acid through a balanced diet . (botanical-online.com)
  • Long story short, I was reading in a natural therapy book about hypothyroidism and L-Tyrosine, B-complex, and Kelp were the top 3 recommended supplements to take. (healthboards.com)
  • L-tyrosine is currently used as an ingredient in dietary supplements and health foods for its purported ability to relieve symptoms of stress, as well as in enteral nutritional products like medical foods. (nutraingredients.com)
  • Amino acid supplements prefaced by the letter L, such as L-Tyrosine, are more similar to the amino acids in the body than those that start with the letter D, with the exception of D-L phenylalanine, which treats chronic pain. (herbalremedies.com)
  • Tyrosine supplements should be taken at bedtime or with a high-carbohydrate meal so it does not compete for absorption with other amino acids. (herbalremedies.com)
  • Although the role of tyrosine phosphorylation in this network is clear, only a limited number of insulin-induced tyrosine phosphorylation sites have been identified. (diabetesjournals.org)
  • Low levels of tyrosine have been associated with low blood pressure, low body temperature, and an under active thyroid. (healthyplace.com)
  • Because of this, people with PKU can have low levels of tyrosine in the body. (webmd.com)
  • Good levels of tyrosine are required to help adapt to stress or anxiety or other problems such as headache because it also influences the synthesis of peptides like enkephalins. (botanical-online.com)
  • Low plasma levels of Tyrosine have been linked with hypothyroidism. (herbalremedies.com)
  • Human and animal research suggests that tyrosine acts as an adaptogen, helping the body adapt to and cope with the effects of physical or psychological stress by minimizing the symptoms brought on by stress. (healthyplace.com)
  • Recent research suggests that tyrosine usage could help treat ED. (healthline.com)
  • A double-blind, placebo-controlled study that enrolled 20 US Marines suggests that tyrosine can improve mental alertness during periods of sleep deprivation. (memorialhealth.com)
  • Tyrosine aminotransferase (or tyrosine transaminase) is an enzyme present in the liver and catalyzes the conversion of tyrosine to 4-hydroxyphenylpyruvate. (wikipedia.org)
  • The body makes tyrosine from another amino acid called phenylalanine . (webmd.com)
  • Phenylalanine, which in turn makes tyrosine, has been used successfully in combination with ultraviolet radiation therapy for darkening the whitened areas in those with vitiligo. (healthyplace.com)
  • He and various colleagues then used PCR amplification and degenerate oligonucleotide probes that recognize the short sequence motifs to identify new tyrosine and serine kinase genes. (asbmb.org)
  • Calculations reveal that the hydroxyl group of tyrosine is more suitable for the proton transfer than hydroxyl groups of other amino acids, such as serine and threonine. (nature.com)
  • N-Benzoyl-L-tyrosine p-nitroanilide (BTPNA) is used as a substrate to identify, differentiate and characterize serine carboxypeptidase(s) and various proteases. (sigmaaldrich.com)
  • Given that tyrosine is made from phenylalanine, restriction of this latter amino acid leads to deficiency of tyrosine. (healthyplace.com)
  • Tyrosine deficiency is rare, according to the University of Maryland Medical Center. (livestrong.com)
  • However, tyrosine plays a role in thyroid function, so tyrosine deficiency is linked to underactive thyroid. (livestrong.com)
  • Tyrosine deficiency also can cause low blood pressure, low body temperature, and restless legs syndrome. (herbalremedies.com)
  • A deficiency of the enzyme in humans can result in what is known as type II tyrosinemia, wherein there is an abundance of tyrosine as a result of tyrosine failing to undergo an aminotransferase reaction to form 4-hydroxyphenylpyruvate. (wikipedia.org)
  • The disease results from a deficiency in hepatic tyrosine aminotransferase. (wikipedia.org)
  • A tyrosine deficiency therefore can contribute to fatigue, mood disorders, cognitive dysfunction, and pain disorders. (ei-resource.org)
  • L-tyrosine is an amino acid that is purported to help boost flagging energy levels or reduce fatigue-related memory problems, often attributed to hormonal insufficiencies due to adrenal fatigue or poor thyroid function. (livestrong.com)
  • L-tyrosine is recommended for its beneficial effect on both adrenal and thyroid hormone production in cases of chronic stress, says 'The Stress Effect' author Richard Weinstein. (livestrong.com)
  • Can L-Tyrosine Restore Thyroid Function? (livestrong.com)
  • Tyrosine influences other hormones such as thyroid , together with iodine, so it is beneficial in people with disorders of the thyroid gland, or alterations of estrogens, such as menopause . (botanical-online.com)
  • The thyroid hormones triiodothyronine (T3) and thyroxine (T4) in the colloid of the thyroid are also derived from tyrosine. (wikipedia.org)
  • In addition, because L-Tyrosine is necessary for the synthesis of thyroid hormone and epinephrine (adrenaline), L-Tyrosine supports healthy glandular function and stress response. (netrition.com)
  • Production of Thyroid Hormones - Tyrosine combines with iodine to form the thyroid hormones. (ei-resource.org)
  • [7] Tyrosine sulfation is catalyzed by tyrosylprotein sulfotransferase (TPST). (wikipedia.org)
  • By knock-out of TPST genes in mice, it may be observed that Tyrosine sulfation has effects on the growth of the mice, such as body weight, fecundity, and postnatal viability. (bionity.com)
  • Tyrosine O-sulfation is an irreversible process in vivo . (bionity.com)
  • It uses material from the Wikipedia article "Tyrosine_sulfation" . (bionity.com)
  • Protein tyrosine phosphatase-1B negatively regulates leptin and insulin signaling, potentially contributing to hormonal resistance. (diabetesjournals.org)
  • Crystal structures of protein-tyrosine phosphatase 1B in complex with compounds bearing a novel isothiazolidinone (IZD) heterocyclic phosphonate mimetic reveal that the heterocycle is highly complementary to the catalytic pocket of the protein. (rcsb.org)
  • By Hunter's recollection, he and his colleagues stumbled on tyrosine phosphorylation through their work on the polyoma DNA tumor virus. (asbmb.org)
  • Folic acid, niacin, vitamin C, and copper are needed to support tyrosine metabolism into these and other important substances, which also include melanin, estrogen molecules, and the enkephalins (natural pain relievers). (healthy.net)
  • Tyrosine also aids in the production of melanin (pigment responsible for hair and skin color) and in the function of organs in the body responsible for making and regulating hormones, including the adrenal, thryroid, and pituitary glands. (healthyplace.com)
  • Given that tyrosine is involved in making melanin, it has been proposed that tyrosine may be a valuable aid in treating vitiligo. (healthyplace.com)
  • Melanin is produced in melanosomes from tyrosine, and it is the substance responsible for the particular coloration of the skin, preventing its depigmentation. (botanical-online.com)
  • Tyrosine is a component in the production of melanin, which is the pigment responsible for hair and skin color. (herbalremedies.com)
  • This book provides coverage, methodology, and laboratory protocols on the more essential aspects of protein tyrosine phosphatase (PTP) function and regulation, including the use of standardized in vitro functional assays, suitable cell systems, and animal and microorganism models. (springer.com)
  • Studying tyrosine kinase expression and regulation in an experimental model system can yield new insights into their role in normal biological and pathophysiological processes. (qiagen.com)
  • There is very limited evidence that the TPST genes are subject to transcriptional regulation and tyrosine O-sulfate is very stable and cannot be easily degraded by mammalian sulfatases. (bionity.com)
  • Mechanistically, we found that direct phosphorylation of tyrosine 566 on NOX4 was critical for this FYN-mediated negative regulation. (jci.org)
  • Here, we have described a mechanism of NLRP3 inflammasome regulation by tyrosine phosphorylation of NLRP3 at Tyr861. (jci.org)
  • For example, the SRC-family kinase regulatory domain requires autophosphorylation for kinase domain activation, while most other intracellular tyrosine kinase families use different regulatory mechanisms. (qiagen.com)
  • It includes an SH2 domain, an SH3 domain and a tyrosine kinase domain. (wikipedia.org)
  • Normally the level of cellular tyrosine kinase phosphorylation is tightly controlled by the antagonizing effect of tyrosine kinase and tyrosine phosphatases. (slideshare.net)
  • Authoritative and practical, Protein Tyrosine Phosphatases: Methods and Protocols aims to aid researchers in better defining the common and individual features of the PTP family members and translating this knowledge into PTP-based therapy for human disease. (springer.com)
  • Therapies that target the TK enzymatic counterparts, the multi-enzyme family of protein tyrosine phosphatases (PTPs), are still lacking despite their undisputed involvement in human diseases. (mdpi.com)
  • Strategies for inducing dimerization by ligand binding are surprisingly diverse, as are mechanisms that couple this event to activation of the intracellular tyrosine kinase domains. (nih.gov)
  • Dimerization of the extracellular regions of RTKs activates the intracellular tyrosine kinase domains (TKDs), which contain a C-lobe (light purple or yellow), N-lobe (dark purple or yellow in the inactive and active states), and an activation loop (dark purple or yellow in the inactive and active states, respectively). (nih.gov)
  • This is primarily due to the fact that tyrosine is a building block for norepinephine and epinephrine, the body's two main stress-related hormones. (healthyplace.com)
  • Prephenate is oxidatively decarboxylated with retention of the hydroxyl group to give p -hydroxyphenylpyruvate, which is transaminated using glutamate as the nitrogen source to give tyrosine and α-ketoglutarate . (wikipedia.org)
  • This enzyme catalyzes the reaction causing the addition of a hydroxyl group to the end of the 6-carbon aromatic ring of phenylalanine , such that it becomes tyrosine. (wikipedia.org)
  • citation needed] Tyrosine ammonia lyase (TAL) is an enzyme in the natural phenols biosynthesis pathway. (wikipedia.org)
  • Learn about the usage, dosage, side-effects of Tyrosine. (healthyplace.com)
  • The effects of tyrosine on cognitive performance during extended wakefulness. (memorialhealth.com)
  • The Dietary Reference Intake (recommended dietary allowance, RDA) for phenylalanine and tyrosine is 33 mg per kilogram of body weight, or 15 mg per pound. (wikipedia.org)
  • Conversion of phenylalanine and tyrosine to its biologically important derivatives. (wikipedia.org)
  • Determination of Phenylalanine and Tyrosine by Liquid Chromatogra. (ingentaconnect.com)
  • One of the oxygen atoms in O 2 is used to hydroxylate the tyrosine molecule to obtain L -DOPA and the other one is used to hydroxylate the cofactor. (wikipedia.org)
  • Tyrosine O-sulfate is a stable molecule and is excreted in urine in animals. (bionity.com)
  • You will find L-tyrosine in tablet, capsule and pill forms. (livestrong.com)
  • T-Cell Protein Tyrosine Phosphatase (TC PTP) is a phospho tyrosine-specific protein phosphatase. (neb.com)
  • To meet their bodies' needs, supplemental tyrosine is given. (webmd.com)
  • Supplemental Tyrosine can be used for reducing stress. (herbalremedies.com)
  • Adding supplemental Tyrosine to the diet can also increase sex drive and eliminate headaches, and there is some evidence that suggests it can be helpful for those suffering from Parkinson s disease as well. (herbalremedies.com)
  • The protein kinase activity associated with pp60 src , the transforming protein of Rous sarcoma virus, was found to phosphorylate tyrosine when assayed in an immunoprecipitate. (pnas.org)
  • Supplemental L-tyrosine helps you if you are suffering from adrenal fatigue with symptoms such as cold hands and feet and depression, Weinstein says. (livestrong.com)
  • MayoClinic.com endocrinologist Todd B. Nippoldt cautions against using unproven remedies such as L-tyrosine to alleviate adrenal fatigue or hormone imbalances. (livestrong.com)
  • Despite the fact that a protein kinase with this activity has not been described before, several observations suggest that pp60 src also phosphorylates tyrosine in vivo . (pnas.org)
  • No enzymatic mechanism of tyrosine sulfate desulfation is known to exist. (bionity.com)
  • Together, our results identify tyrosine phosphorylation as an important regulatory mechanism for NLRP3 that prevents aberrant inflammasome activation. (jci.org)
  • In a similar mechanism of aspartate transaminase, the lysine that forms the initial imine to PLP later acts as the base that attacks the tyrosine in transimination. (wikipedia.org)
  • Chapters covering state-of-the-art technical approaches suitable to decipher the physiologic roles of PTPs, and their involvement in tissue-specific functions, are also included, which will be of utility for both newcomers and experienced researchers in the field of tyrosine- and phosphoinositide- phosphorylation/dephosphorylation. (springer.com)
  • Tyrosine is also involved in the synthesis of enkephalins, substances that have pain-relieving effects in the body. (healthyplace.com)
  • N-Acetyl Tyrosine is an acetylated derivative of the essential amino acid L-tyrosine. (patientslikeme.com)
  • By providing the raw material for the production of catecholamines, tyrosine may provide relief from stress and forms of depression where lack of motivation is prominent. (ei-resource.org)
  • Humans often get tyrosine from foods high in protein. (healthline.com)
  • The activation of c-Src causes the dephosphorylation of the tyrosine 527. (wikipedia.org)