Son of Sevenless Protein, Drosophila: A guanine nucleotide exchange factor from DROSOPHILA. Sevenless refers to genetic mutations in DROSOPHILA that cause loss of the R7 photoreceptor which is required to see UV light.Son of Sevenless Proteins: A class of RAS GUANINE NUCLEOTIDE EXCHANGE FACTORS that are genetically related to the Son of Sevenless gene from DROSOPHILA. Sevenless refers to genetic mutations in DROSOPHILA that cause loss of the R7 photoreceptor which is required to see UV light.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.GuanineSOS1 Protein: A mammalian homolog of the DROSOPHILA SON OF SEVENLESS PROTEIN. It is a guanine nucleotide exchange factor for RAS PROTEINS.Guanine NucleotidesGuanine Nucleotide Exchange Factors: Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS.Receptor Protein-Tyrosine Kinases: A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.Photoreceptor Cells, Invertebrate: Specialized cells in the invertebrates that detect and transduce light. They are predominantly rhabdomeric with an array of photosensitive microvilli. Illumination depolarizes invertebrate photoreceptors by stimulating Na+ influx across the plasma membrane.Protein Tyrosine Phosphatases: 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.Eye ProteinsMolecular Sequence Data: 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.Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.ras Guanine Nucleotide Exchange Factors: A family of GUANINE NUCLEOTIDE EXCHANGE FACTORS that are specific for RAS PROTEINS.Signal Transduction: 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.Eye: The organ of sight constituting a pair of globular organs made up of a three-layered roughly spherical structure specialized for receiving and responding to light.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Amino Acid Sequence: 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.Tyrosine 3-Monooxygenase: An enzyme that catalyzes the conversion of L-tyrosine, tetrahydrobiopterin, and oxygen to 3,4-dihydroxy-L-phenylalanine, dihydrobiopterin, and water. EC 1.14.16.2.Protein Binding: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Protein Tyrosine Phosphatases, Non-Receptor: 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.src Homology Domains: 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.ras Proteins: Small, monomeric GTP-binding proteins encoded by ras genes (GENES, RAS). The protooncogene-derived protein, PROTO-ONCOGENE PROTEIN P21(RAS), plays a role in normal cellular growth, differentiation and development. The oncogene-derived protein (ONCOGENE PROTEIN P21(RAS)) can play a role in aberrant cellular regulation during neoplastic cell transformation (CELL TRANSFORMATION, NEOPLASTIC). This enzyme was formerly listed as EC 3.6.1.47.Mutation: 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.GRB2 Adaptor Protein: 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).Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Guanine Deaminase: An enzyme that catalyzes the deamination of guanine to form xanthine. EC 3.5.4.3.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Adaptor Proteins, Signal Transducing: 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 enzymesPhosphotyrosine: 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.Photoreceptor Cells: Specialized cells that detect and transduce light. They are classified into two types based on their light reception structure, the ciliary photoreceptors and the rhabdomeric photoreceptors with MICROVILLI. Ciliary photoreceptor cells use OPSINS that activate a PHOSPHODIESTERASE phosphodiesterase cascade. Rhabdomeric photoreceptor cells use opsins that activate a PHOSPHOLIPASE C cascade.Supraoptic Nucleus: Hypothalamic nucleus overlying the beginning of the OPTIC TRACT.Enzyme Activation: 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.Proteins: 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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Receptors, Peptide: Cell surface receptors that bind peptide messengers with high affinity and regulate intracellular signals which influence the behavior of cells.Proto-Oncogene 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.Recombinant Fusion Proteins: 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.Membrane Proteins: 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.Guanosine Triphosphate: Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.Drosophila melanogaster: A species of fruit fly much used in genetics because of the large size of its chromosomes.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Kinetics: The rate dynamics in chemical or physical systems.Protein Tyrosine Phosphatase, Non-Receptor Type 11: 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.Receptor, Epidermal Growth Factor: 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.Genes, Insect: The functional hereditary units of INSECTS.Rho Guanine Nucleotide Exchange Factors: Signaling proteins which function as master molecular switches by activating Rho GTPases through conversion of guanine nucleotides. Rho GTPases in turn control many aspects of cell behavior through the regulation of multiple downstream signal transduction pathways.GTP-Binding Proteins: Regulatory proteins that act as molecular switches. They control a wide range of biological processes including: receptor signaling, intracellular signal transduction pathways, and protein synthesis. Their activity is regulated by factors that control their ability to bind to and hydrolyze GTP to GDP. EC 3.6.1.-.Protein Structure, Tertiary: 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.Guanosine Diphosphate: A guanine nucleotide containing two phosphate groups esterified to the sugar moiety.Protein Tyrosine Phosphatase, Non-Receptor Type 6: 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.PhosphoproteinsProto-Oncogene Proteins c-raf: A ubiquitously expressed raf kinase subclass that plays an important role in SIGNAL TRANSDUCTION. The c-raf Kinases are MAP kinase kinase kinases that have specificity for MAP KINASE KINASE 1 and MAP KINASE KINASE 2.Protein Tyrosine Phosphatase, Non-Receptor Type 1: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Cells, Cultured: 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.Transfection: 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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Enhancer Elements, Genetic: Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.Lymphocyte Specific Protein Tyrosine Kinase p56(lck): 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.

*Son of Sevenless

"An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro". Cell. 73 (1): 169- ... Son of sevenless Functions Downstream of the sevenless and EGF Receptor Tyrosine Kinases". Cell. 64 (1): 39-48. doi:10.1016/ ... In cell signalling, Son of Sevenless (SOS) refers to a set of genes encoding guanine nucleotide exchange factors that act on ... SOS (and other guanine nucleotide exchange factors) act by binding Ras-GTPases and forcing them to release their bound ...

*List of MeSH codes (D12.644)

... son of sevenless proteins MeSH D12.644.360.325.300.700.700.600 --- son of sevenless protein, drosophila MeSH D12.644.360.325. ... rab5 gtp-binding proteins MeSH D12.644.360.525.450 --- ral gtp-binding proteins MeSH D12.644.360.525.462 --- ran gtp-binding ... cdc2 protein kinase MeSH D12.644.360.275 --- eif-2 kinase MeSH D12.644.360.287 --- focal adhesion protein-tyrosine kinases MeSH ... p120 gtpase activating protein MeSH D12.644.360.325.150.750 --- rgs proteins MeSH D12.644.360.325.225 --- guanine nucleotide ...

*SOS1

RAS genes (e.g., MIM 190020) encode membrane-bound guanine nucleotide-binding proteins that function in the transduction of ... In Drosophila, the protein encoded by the 'son of sevenless' gene (Sos) contains a domain that shows sequence similarity with ... Liu SK, McGlade CJ (Dec 1998). "Gads is a novel SH2 and SH3 domain-containing adaptor protein that binds to tyrosine- ... Son of sevenless homolog 1 is a protein that in humans is encoded by the SOS1 gene. ...

*GRB2

... protein is a major FGF-stimulated tyrosine phosphorylated 90-kDa protein which binds to the SH2 domain of GRB2". Biochemical ... "Engagement of the T lymphocyte antigen receptor regulates association of son-of-sevenless homologues with the SH3 domain of ... a guanine nucleotide-releasing protein expressed ubiquitously, binds to the Src homology 3 domains of CRK and GRB2/ASH proteins ... "Phosphorylation of receptor protein-tyrosine phosphatase alpha on Tyr789, a binding site for the SH3-SH2-SH3 adaptor protein ...

*PLCG1

The SH2 domains bind phosphorylated tyrosine residues on target proteins via their FLVR sequence motifs, activating the ... "Engagement of the T lymphocyte antigen receptor regulates association of son-of-sevenless homologues with the SH3 domain of ... For example, when activated by SRC, the encoded protein causes the Ras guanine nucleotide exchange factor RASGRP1 to ... is a binding partner for c-Src family protein-tyrosine kinases". Current Biology. 6 (8): 981-8. doi:10.1016/s0960-9822(02)00642 ...

*GTP-binding protein regulators

Guanine nucleotide exchange factor. *EIF2B. *Son of Sevenless. *Ras-GRF1. .mw-parser-output .nobold{font-weight:normal}. FGD. * ... Tyrosine:. *protein tyrosine phosphatase: Receptor-like protein tyrosine phosphatase. *Sh2 domain-containing protein tyrosine ... GTP-binding protein regulators regulate G proteins in several different ways. Small GTPases act as molecular switches in ... Another class of regulatory proteins, the Guanosine nucleotide dissociation inhibitors (GDIs), bind to the GDP-bound form of ...
Insulin receptor signaling acutely stimulates GTP loading of p21ras, apparently by mobilizing complexes of Grb2 and the guanine nucleotide exchangers Son-of-sevenless (Sos) 1 and 2 to associate with tyrosine-phosphorylated proteins in the plasma membrane. Here we show that in 32P-labeled 3T3-L1 adipocytes the elevated cellular concentrations of [32P]GTP-bound p21ras in response to insulin return to near basal levels after 20-30 min of hormone stimulation, while insulin receptors remain activated. Lysates of such desensitized cells were quantitatively immunoprecipitated with an antiserum recognizing both Sos1 and Sos2 proteins or a specific anti-Sos2 antiserum. Immunoblot analysis of these precipitates revealed that insulin causes a marked hyperphosphorylation of Sos1 and a 50% decrease in Grb2 associated with Sos proteins under these conditions. Similarly, anti-Grb2 immunoprecipitates of ...
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 ...
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 ...
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 ...
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 ...
The role of Shc-GRB2-Sos and Ras in signal transduction by Gq-coupled receptors, such as the AT1 receptor, is unclear. Importantly, tyrosine phosphorylation of Shc61 82 106 and activation of Ras by angiotensin II were recently demonstrated.107 Tyrosine phosphorylation of a linker protein called Shc appears to be an important mechanism used by all G protein-coupled receptors on the basis of studies to date.108 For Gi-coupled receptors, a pathway for activation of Ras and ERK1/2 has been proposed (Fig 2⇑)106 107 108 in which release of G-protein βγ subunits from G protein-coupled receptors stimulates downstream events leading to tyrosine phosphorylation of Shc.109 c-Src has been proposed as a likely candidate.108 110 111 Additional signal mediators that may be required include PI 3-K and a protein tyrosine phosphatase.108 Once Shc is tyrosine-phosphorylated, it now binds GRB2 via SH2 domain interactions (Fig ...
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. ...
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 ...
Increasing evidence supports the hypothesis that tannic acid, a plant polyphenol, exerts anticarcinogenic activity in chemically induced cancers. In the present study, tannic acid was found to strongly inhibit tyrosine kinase activity of epidermal growth factor receptor (EGFr) in vitro (IC50 = 323 nM). In contrast, the inhibition by tannic acid of p60c-src tyrosine kinase (IC50 = 14 μM) and insulin receptor tyrosine kinase (IC50 = 5 μM) was much weaker. The inhibition of EGFr tyrosine kinase by tannic acid was competitive with respect to ATP and non-competitive with respect to peptide substrate. In cultured cells, growth factor-induced tyrosine phosphorylation of growth factor receptors, including EGFr, platelet-derived growth factor receptor, and basic fibroblast growth factor receptor, was inhibited by tannic acid. No inhibition of insulin-induced tyrosine phosphorylation of insulin receptor and ...
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 ...
TY - JOUR. T1 - Regulation in the targeting of TRAIL receptor 1 to cell surface via GODZ for TRAIL sensitivity in tumor cells. AU - Oh, Yumin. AU - Jeon, Y. J.. AU - Hong, G. S.. AU - Kim, I.. AU - Woo, H. N.. AU - Jung, Y. K.. PY - 2012/7. Y1 - 2012/7. N2 - Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors, TRAIL-R1 (DR4) and TRAIL-R2 (DR5), promote the selective clearing of various malignancies by inducing apoptosis, holding the promise as a potent therapeutic agent for anticancer. Though DR4 and DR5 have high sequence similarity, differential regulation of both receptors in human tumor cells remains largely unexplored. Here, we repot that golgi-specific Asp-His-His-Cys (DHHC) zinc finger protein (GODZ) regulates TRAIL/DR4-mediated apoptosis. Using the SOS protein recruitment-yeast two-hybrid screening, we isolated GODZ that interacted with the death domain of DR4. GODZ binds to DR4, but not to DR5, through the DHHC and the C-terminal transmembrane domain. ...
TY - JOUR. T1 - Purification and characterization of a protein tyrosine phosphatase which dephosphorylates the nicotinic acetylcholine receptor. AU - Mei, Lin. AU - Huganir, Richard L.. PY - 1991/12/1. Y1 - 1991/12/1. N2 - The nicotinic acetylcholine receptor (nAChR) is phosphorylated to a high stoichiometry on tyrosine residues both in vitro and in vivo. Moreover, tyrosine phosphorylation has been shown to regulate the functional properties of the receptor. We report here the purification and characterization of a protein tyrosine phosphatase that dephosphorylates tyrosine-phosphorylated nAChR from Torpedo electroplax, a tissue highly enriched in the nAChR. The 32P-labeled tyrosine phosphorylated nAChR was used as a substrate to monitor the enzyme activity during purification. The protein tyrosine phosphatase activity was purified using three consecutive cation-exchange columns ...
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 ...
Granulocyte colony-stimulating factor (G-CSF) is the major regulator of granulopoiesis and acts through binding to its specific receptor (G-CSF-R) on neutrophilic granulocytes. Previous studies of signaling from the 4 G-CSF-R cytoplasmic tyrosine residues used model cell lines that may have idiosyncratic, nonphysiological responses. This study aimed to identify specific signals transmitted by the receptor tyrosine residues in primary myeloid cells. To bypass the presence of endogenous G-CSF-R, a chimeric receptor containing the extracellular domain of the epidermal growth factor receptor in place of the entire extracellular domain of the G-CSF-R was used. A series of chimeric receptors containing tyrosine mutations to phenylalanine, either individually or collectively, was constructed and expressed in primary bone marrow cells from G-CSF-deficient mice. Proliferation and differentiation responses of receptor-expressing bone marrow cells stimulated by ...
The reaction product of nitric oxide and superoxide, peroxynitrite, is a potent biological oxidant. The most important oxidative protein modifications described for peroxynitrite are cysteine-thiol oxidation and tyrosine nitration. We have previously demonstrated that intrinsic heme-thiolate (P450)-dependent enzymatic catalysis increases the nitration of tyrosine 430 in prostacyclin synthase and results in loss of activity which contributes to endothelial dysfunction. We here report the sensitive peroxynitrite-dependent nitration of an over-expressed and partially purified human prostacyclin synthase (3.3 μM) with an EC50 value of 5 μM. Microsomal thiols in these preparations effectively compete for peroxynitrite and block the nitration of other proteins up to 50 μM peroxynitrite. Purified, recombinant PGIS showed a half-maximal nitration by 10 μM 3-morpholino sydnonimine (Sin-1) which increased in the presence of bicarbonate, and was only marginally ...
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 ...
After the intraportal injection of EGF, the EGF receptor (EGFR) is rapidly internalized into hepatic endosomes where it remains largely receptor bound (Lai et al., 1989. J. Cell Biol. 109:2751-2760). In the present study, we evaluated the phosphotyrosine content of EGFRs at the cell surface and in endosomes in order to assess the consequences of internalization. Quantitative estimates of specific radioactivity of the EGFR in these two compartments revealed that tyrosine phosphorylation of the EGFR was observed at the cell surface within 30 s of ligand administration. However, the EGFR was also highly phosphorylated in endosomes reaching levels of tyrosine phosphorylation significantly higher than those of the cell surface receptor at 5 and 15 min after EGF injection. A 55-kD tyrosine phosphorylated polypeptide (pyp55) was observed in association with the EGFR at the cell surface within 30 s of EGF injection. The protein was also found in ...
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. ...
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 ...
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 ...
Peroxynitrite formation in vivo is implicated in numerous human diseases and there is considerable interest in the use of antioxidants and natural products such as thiols as peroxynitrite scavengers. We therefore investigated the effects of a recently identified constituent of onions, 3-mercapto-2-methylpentan-1-ol (3-MP), for its ability to inhibit peroxynitrite-mediated processes in vitro and using cultured human cells and compared its effectiveness against glutathione. 3-MP significantly inhibited peroxynitrite-mediated tyrosine nitration and inactivation of α1-antiproteinase to a greater extent than glutathione at each concentration tested (15-500μM). 3-MP also inhibited peroxynitrite-induced cytotoxicity, intracellular tyrosine nitration, and intracellular reactive oxygen species generation in human HepG2 cells in culture to a greater extent than glutathione. These data suggest that 3-MP has the potential to act as an inhibitor of ONOO--mediated processes in vivo and ...
The data generated in this study support a causal association between protein tyrosine phosphorylation during capacitation of mouse spermatozoa and the ability of these cells to bind to the zona pellucida. Although there have been many failed attempts to characterise the molecular basis of sperm-zona recognition, all previous approaches to this problem were predicated on the notion of a permanently expressed receptor. This study introduces the concept of a receptor complex that is assembled on the sperm surface as a consequence of the tyrosine phosphorylation events associated with sperm capacitation. This concept therefore confirms earlier biological data suggesting that sperm-egg recognition is capacitation dependent (Swenson and Dunbar, 1982). As a result of this study, we can now suggest a molecular basis for this association.. Initial anti-phosphotyrosine immunolabelling of fixed spermatozoa recovered from the zona pellucida yielded the ...
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 ...
Relapse occurred in 7 (44%) of the 16 patients who stopped tyrosine kinase inhibitor treatment at the time of complete remission, 4 (33%) of the 12 who stopped treatment after additional cycles, and 1 (13%) of the 8 who were still receiving a tyrosine kinase inhibitor. The median time from complete remission to relapse was 7.9 months (range, 3-32 months). Relapse occurred at a previously involved metastatic site in 5 of 12 patients with relapse. Thus, of the 28 patients who stopped tyrosine kinase inhibitor treatment, 17 (61%) remained in complete remission after a median follow-up of 8.5 months (range, 0.3-39.1 months). Tyrosine Kinase Inhibitor Plus Local Treatment. A total of 28 patients (44%) achieved complete remission with a tyrosine kinase inhibitor and local therapy (Fig. 2), consisting of surgery in 22 (79%), radiofrequency ablation in 2 (7%), and radiation therapy in 4 (14%). Most patients received local therapy ...
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 ...
TY - JOUR. T1 - Inhibitory role of Src family tyrosine kinases on Ca2+-dependent insulin release. AU - Cheng, Haiying. AU - Straub, Susanne G.. AU - Sharp, Geoffrey W G. PY - 2007/3. Y1 - 2007/3. N2 - Both neurotransmitter release and insulin secretion occur via regulated exocytosis and share a variety of similar regulatory mechanisms. It has been suggested that Src family tyrosine kinases inhibit neurotransmitter release from neuronal cells (H. Ohnishi, S. Yamamori, K. Ono, K. Aoyagi, S. Kondo, and M. Takahashi. Proc Natl Acad Sci USA 98: 10930-10935, 2001). Thus the potential role of Src family kinases in the regulation of insulin secretion was investigated in this study. Two structurally different inhibitors of Src family kinases, SU-6656 and PP2, but not the inactive compound, PP3, enhanced Ca 2+-induced insulin secretion in both rat pancreatic islets and INS-1 cells in a concentration-dependent and time-dependent manner. Furthermore, Src family kinase-mediated insulin ...
Looking for online definition of NCK tyrosine kinase, NCKalpha in the Medical Dictionary? NCK tyrosine kinase, NCKalpha explanation free. What is NCK tyrosine kinase, NCKalpha? Meaning of NCK tyrosine kinase, NCKalpha medical term. What does NCK tyrosine kinase, NCKalpha mean?
1. Neri DF, Wiegmann D, Stanny RR, et al. The effects of tyrosine on cognitive performance during extended wakefulness. Avit Space Environ Med. 1995;66:313-319. 2. Eisenberg MD, Asnis GM, van Praag HM, et al. Effect of tyrosine on attention deficit disorder with hyperactivity. J Clin Psychiatry. 1988;49:193-195. 3. Reimherr FW, Wender PH, Wood RD, et al. An open trial of L-tyrosine in the treatment of attention deficit disorder, residual type. Am J Psychiatry. 1987;144:1071-1073. 4. Wood RD, Reimherr FW, Wender PH, et al. Amino acid precursors for the treatment of attention deficit disorder, residual type. Psychopharmacol Bull. 1985;21:146-149. 5. Gibson C, Gelenberg A. Tyrosine for the treatment of depression. Adv Biol Psychiatry. 1983;10:148-159. 6. Gelenberg AJ, Wojcik JD, Falk WE, et al. Tyrosine for depression: a double-blind trial. J Affect Disord. 1990; 19:125-132. 7. Neri DF, Wiegmann D, Stanny RR, ...
Tyrosine phosphorylation of paxillin by the focal adhesion kinase (FAK) has been implicated as a signal transduction mechanism associated with cell adhesion and cytoskeletal reorganization. The potential role of serine phosphorylation of paxillin in these events has not been well characterized. In this study we have examined the phosphorylation profile of paxillin both invitro and invivo. By using glutathione S-transferase-paxillin fusion proteins in precipitation-kinase assays invitro we observed that a fusion protein spanning amino acid residues 54-313 of paxillin, and containing a FAK-binding site, precipitated substantial serine kinase activity as well as FAK activity from a smooth-muscle lysate. Together these kinases phosphorylated paxillin on tyrosine residue 118, a site that has been identified previously as a target for FAK phosphorylation, and on serine residues 188 and/or 190. The binding site for the serine kinase, the identity of which is ...
A biofilm is a complex community of cells enveloped in a self-produced polymeric matrix. Entry into a biofilm is exquisitely controlled at the level of transcription and in the Gram-positive organism Bacillus subtilis it requires the concerted efforts of three major transcription factors. Here, we demonstrate that in addition to transcriptional control, B. subtilis utilizes post-translational modifications to control biofilm formation; specifically through phosphorylation of tyrosine residues. Through our work we have assigned novel roles during biofilm formation to two proteins; the protein tyrosine kinase PtkA and the protein tyrosine phosphatase PtpZ. Furthermore by introducing amino acid point mutations within the catalytic domains of PtkA and PtpZ we have identified that the kinase and phosphatase activities, respectively, are essential for function. PtkA contains a conserved C-terminal tyrosine cluster that is the site ...
Protein-tyrosine kinase C-terminal Src kinase (Csk) was originally purified as a kinase for phosphorylating Src and other Src family kinases. The phosphorylation of a C-terminal tyrosine residue of Src family kinases suppresses their kinase activity. Therefore, most physiological studies regarding Csk function have been focused on Csk as a negative regulator of Src family tyrosine kinases and as a potential tumor suppressor. Paradoxically, the protein levels of Csk were elevated in some human carcinomas. In this report, we show that eukaryotic elongation factor 2 (eEF2) is a new protein substrate of Csk and could locate in the nucleus ...
250 µCi quantities of L-[Ring-3,5-3H]-Tyrosine are available for your research. Application of [3H]Tyrosine can be found in: kyotorphin transport and metabolism in rat and mouse neonatal astrocytes in brain research, neuropeptide Y-induced enhancement of the evoked release of newly synthesized dopamine in rat striatum in neuropharmacology, effect of metals on ß-actin and total protein synthesis in cultured human intestinal epithelial cells in toxicology, etc. ...
In contrast to receptor protein tyrosine kinases and associated downstream signaling events in the cardiovascular system, the protein tyrosine phosphatases that potentially function as counter-regulatory agents have been less extensively investigated. Thus, the present study addressed the functional role of the ubiquitous phosphatase PTP1B in cultured rat aortic smooth muscle cells and in carotid arteries. In addition to targeting the PDGF receptor, PTP1B has been reported to induce dephosphorylation of several other receptor tyrosine kinases, including the insulin receptor,17 epidermal growth factor receptor,30 and IGF-1 receptor.15. We report for the first time that PTP1B targets PDGF- or FGF-induced cell motility and proliferation in vitro and neointima formation in vivo. It is interesting to note a recent study indicating that signaling events downstream of the PDGF receptor were not significantly altered in fibroblasts genetically lacking PTP1B, ...
The K-ras oncogene is a GTPase switch protein which is responsible for activating intracellular signalling pathways in response to extracellular growth signals. Activation of the receptor tyrosine kinase by an external signal molecule causes the Grb-2 adaptor protein to bind to the Ras guanine nucleotide exchange factor (GEF). This stimulates Ras to exchange its bound GDP for GTP and so activate several downstream signalling pathways which lead to cell division. GTPase-activating proteins (GAPs) inactivate Ras by stimulating it to hydrolyse its bound GTP; the inactivated Ras remains tightly bound to GDP. Guanine nucleotide exchange factors (GEFs) activate Ras by stimulating it to give up its GDP; the concentration of GTP in the cytosol is 10 times greater than the concentration of GDP, and Ras rapidly binds GTP once GDP has been ejected. Any mutation which changes the amino acid glycine at position 12 in the Ras protein ...
The K-ras oncogene is a GTPase switch protein which is responsible for activating intracellular signalling pathways in response to extracellular growth signals. Activation of the receptor tyrosine kinase by an external signal molecule causes the Grb-2 adaptor protein to bind to the Ras guanine nucleotide exchange factor (GEF). This stimulates Ras to exchange its bound GDP for GTP and so activate several downstream signalling pathways which lead to cell division. GTPase-activating proteins (GAPs) inactivate Ras by stimulating it to hydrolyse its bound GTP; the inactivated Ras remains tightly bound to GDP. Guanine nucleotide exchange factors (GEFs) activate Ras by stimulating it to give up its GDP; the concentration of GTP in the cytosol is 10 times greater than the concentration of GDP, and Ras rapidly binds GTP once GDP has been ejected. Any mutation which changes the amino acid glycine at position 12 in the Ras protein ...
Actins; Animals; Chemotaxis; Cyclic AMP; Cytokinesis; Dictyostelium; Genetic techniques; Guanine nucleotide exchange factors; Light; Models; Biological; Myosin type II; Myosins; Phosphorylation; Protein binding; Protein structure; Tertiary; Proteins; Recombinant fusion proteins; Research; Research Support; Chemistry; Metabolism; Physiology; Ras guanine nucleotide exchange factors; Ras proteins; REF 2014 ...
Actins; Animals; Chemotaxis; Cyclic AMP; Cytokinesis; Dictyostelium; Genetic techniques; Guanine nucleotide exchange factors; Light; Models; Biological; Myosin type II; Myosins; Phosphorylation; Protein binding; Protein structure; Tertiary; Proteins; Recombinant fusion proteins; Research; Research Support; Chemistry; Metabolism; Physiology; Ras guanine nucleotide exchange factors; Ras proteins; REF 2014 ...
In Dictyostelium, a transient increase in intracellular cGMP is important for cytoskeletal rearrangements during chemotaxis. There must be cGMP-binding proteins in Dictyostelium that regulate key cytoskeletal components after treatment with chemoattractants, but to date, no such proteins have been identified. Using a bioinformatics approach, we have found four candidate cGMP-binding proteins (GbpA-D). GbpA and -B have two tandem cGMP-binding sites downstream of a metallo beta-lactamase domain, a superfamily that includes cAMP phosphodiesterases. GbpC contains the following nine domains (in order): leucine-rich repeats, Ras, MEK kinase, Ras guanine nucleotide exchange factor N-terminal (RasGEF-N), DEP, RasGEF, cGMP-binding, GRAM, and a second cGMP-binding domain. GbpD is related to GbpC, but is much shorter; it begins with the RasGEF-N domain, and lacks the DEP domain. Disruption of the gbpC gene results in loss of all high-affinity ...
The protein encoded by this gene is a member of the Ras guanyl nucleotide-releasing protein (RasGRP) family of Ras guanine nucleotide exchange…
Inhibition of full-length human KRas4B (amino acids 1 to 188)-SOS interaction assessed as inhibition of SOS-mediated nucleotide release ...
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
A reduced collagen amount in arterial walls is one of the prominent pathological features of CAs,2,3 which is confirmed also in the present study (supplemental Figure I). Excessive collagenolysis in CA walls is induced by the imbalanced expression between MMPs and TIMPs,7 and between cathepsins and cystatin C.5 Decreased collagen biosynthesis in CA walls, the other important aspect of degenerative changes in CA walls, was observed in this study. Expression of procollagen type I and III was downregulated in CA walls at the transcriptional level (Figure 1). Some studies showed a reduced level of type-III collagen in patients with CAs.24,25 Although no mutations were found in the type-III procollagen gene in patients with CAs,26,27 reduced production of type-III collagen may be derived from impaired regulation of gene expression of the type-III procollagen gene.. Collagens must be crosslinked to exhibit the normal physical properties of tensile strength. LOX catalyzes the final enzymatic step for ...
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Pragniemy serdecznie zaprosić Państwa na seminarium doktoranckie Informatyki Społecznej, które odbędzie się w najbliższy poniedziałek, 20.06.2016, o godz.15:30 w sali 110A ...
Rabbit polyclonal GODZ antibody validated for WB, IHC, ICC/IF and tested in Human, Mouse and Rat. Referenced in 6 publications and 1 independent review…
Figure 2: Examples of the probability distribution (a, b, and c) and trace plots (d, e, and f) of reaction rates 2 (which indicates the simultaneous recruitment of Shc and Grb2-SOS complex from the cytosol to the cell membrane by the recruitment of EGFR (a and d)), 16 (which shows the activation of MEK proteins by active Raf (b and e)), and 38 (which refers to the dissociation of active ERK and RSK complex (c and f)) of Model 2 under ...
Several approaches to dating were attempted, and our research on this topic continues. At Preveli 2, east of the Preveli Gorge, Palaeolithic artifacts are associated with a flight of marine terraces resulting from relatively high sea levels in the Pleistocene that were preserved by subsequent rock uplift. The lowest late Pleistocene marine terraces resulting from high stands of the sea at Preveli (14 ± 1 masl) and Schinaria (21 ± 1 masl) have 2-sigma calibrated radiocarbon ages of 45,400 ± 1,600 and 49,120 ± 2,890 years b.p., respectively, and are correlated with Marine Isotope Stages 3.3 and 3.4, both eustatic high stands. The higher terraces, at 59 and 96 masl, are unquestionably older. How much older? Assuming similar rates of rock uplift (1.4 ± 0.1 m/kyr) determined from the age-elevation relationships of the dated terraces at 14 and 21 masl, it is possible to estimate the approximate ages of the terraces associated with artifacts. This correlation provides an approximate age for the ...
Requires iron(II) for activity. Unlike the proline hydroxylases involved in collagen biosynthesis [EC 1.14.11.2 (procollagen-proline dioxygenase) and EC 1.14.11.7 (procol
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I have two sons that I kiss every day Im with them. Theyre not babies, either. My oldest son is 9 and my youngest son is 6. I give them kisses regardless of whether it be in public or private. Im proud of the fact that they arent worried about how it looks to strangers or who sees them puckering up to lay one on their dads scruffy face. I like when both of them grab the patch of hair on my face that passes for a beard and tell me I need to shave because its scratchy when I give them a kiss good night. Being a very affectionate human myself, I dont see this as anything but showing my boys that I love them. But when I look at, and I mean REALLY look at, fathers and how they interact with their sons when Im in public, I feel like Im in the minority.. Comedian Rob Delaney recently posted something on his Tumblr account that was printed in an Australian magazine named Smith Journal about men kissing their boys which really struck a chord in me. ...
Why does my sons breath smell like feces? I noticed today that my 6 year old sons breath ... Why is my sons breath suddenly smelling like poop?
Why does my sons breath smell like feces? I noticed today that my 6 year old sons breath ... Why is my sons breath suddenly smelling like poop?
Akbar and his sons Akbar had three sons Salim, Murad and Daniyal. All the three were big alcoholics and wasted their young life in intoxication. Like they say no plants can grown under a huge banyan tree, Akbar was a huge banyan tree that never allowed his sons to come out of his shadow. This…
A: At some point you will really have to decide to go drugless in helping your son as drugs dont heal anything that God created. That drug hes taking that made him gain 40...
... serve as a wonderful model on how to transmit our rich heritage effectively, tailor-made to each childs capacity and unique way of learning.
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My son is coughing - My two year old son has had a dry cough for nearly two months now, and his ped says its a bronchitis infection or so and......
The woman whose struggle to help her son overcome a gross deformity touched millions in the film Mask is facing another deadly battle: Her other son has AIDS.Rusty Mason says she will fight for
Im due to deliver in five weeks and my husband and I are still debating whether to circumcise our son. I would really prefer not to have our son circumcised.
... Las frutas con menos calorias. Partes del aparato fonador Cuerdas vocales son musculos las, que hacer cuando un nino convulsiona por fiebre alta.
My son who is 5 years old has shown signs of allergy to some dogs but not others. We would love to have a family pet dog but also do not want our sons health to suffer. I have done a lot of research to find out which breed would be bes
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Actress January Jones admits she may not be the best man to raise a son. Jones made headlines in May when she said her 4-year-old son, Xander, already has
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WINSTON-SALEM, N.C. -- Its been six months, but Ebony Aiken says the pain of losing her son Nasir is still fresh. Some days I wake up,
Dear Larry:Well, son, you probably thought you were long done with lectures from your old man, but not quite. I`d rather not give this one and I`m sure you would rather not hear it, but I cannot
A mother of a child with a disability shares how her landlord shows no compassion or understanding to the challenges her son has faced and the many doctors and interventions necessary to help him.
My 6 week old son is constipated. I already tried Karo syrup but it didnt work.... Ive tried stinking in the thermometer that didnt work either.... it brakes
My 7 month old son wants to be held all the time. He wont let me put him down without crying, even if its just for a couple minutes while I use the restroom.
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My son has many of the behaviors in the social, emotional and sensory-seeking categories but a few others as well. He is 6-1/2 and one year ago (the summer
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וישׁמעאל And Ishmael בנו his son בן old, שׁלשׁ thirteen עשׂרה thirteen שׁנה years בהמלו when he was circumcised את בשׂר in the flesh ערלתו׃ of his foreskin. IHOT Genesis 17:25
The Well Done, Son! Guy trope as used in popular culture. Our hero may be a perfectly Nice Guy, respectable, successful, a loving husband and a good father …
Autism. That one word, uttered by a white-coated doctor during the spring of 2007, was all it took to turn my life upside down. Since my sons birth three and a half years previously, I had been lovin...
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A couple were devastated last night after being denied the chance to create a designer baby to help save their seriously ill son.
Christine Stephenson recently shared her husbands text to his friends after they ostracized his autistic son, and the strongly-worded messages quickly went viral.
The woman youve all been asking us about says she still hasnt heard from her son. She says his boyfriend has passed away and she is a realist, but as a mother she has to have hope.
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hi i have a stepson who is 3 and i really want to adopt him i have been his stepmother for two years and have been his consistent mother figure. over
the traitors amongst his Ummah. that is why he was born Karbala. that is what he will say Husayn. that is who he will avenge. ...
Jakob Goldenthal confirmed Eloni was none other than Elioneiai son of Caiaphas. The children of Elioneiai were his son Jonathias and his daughter Martha. Martha married Jeshua ben Gamaliel of the House of Phiabi. Therefore the son of Eloni from the Chain of Transmission being referred to as the Kahana, it would stand to reason was actually none other than Jeshua ben Gamaliel. At that moment in history my family obtained officially the title of Kahana.
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well....i already tried that lb....drank at my son all the time...not only did he just get worse...it really was drinking poisen and hopeing the other
A DEDICATED Kirkcaldy family are preparing their young son for a serious operation they hope will give him a much brighter future.
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Los sulfitos son un tipo de conservante de alimentos que pueden provocar dificultades para respirar en algunas personas asmáticas.
Squamous cell carcinoma of the skin in Mineola has multiple risk factors, but the greatest risk factor is sun exposure. Sun: For those who have a long history of sun exposure, the risk of SCC is very high. Individuals who have lived in the Southern USA have a greater chance of developing SCC than those who live in the Northern parts of the country. Worldwide, SCC is again more common in the sunny areas.
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GRB2 (Growth factor receptor-bound protein 2)GRB2 (Growth factor receptor-bound protein 2)

Growth factor receptor-bound protein 2), Authors: Gagani Athauda, Donald P Bottaro. Published in: Atlas Genet Cytogenet Oncol ... A Drosophila SH2-SH3 adaptor protein implicated in coupling the sevenless tyrosine kinase to an activator of Ras guanine ... The two GRB2 SH3 domains bind to the proline-rich regions of the guanine nucleotide releasing factor son of sevenless (SOS-1) ... An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro.. ...
more infohttp://atlasgeneticsoncology.org/Genes/GC_GRB2.html

Disassembly of Son-of-sevenless proteins from Grb2 during p21ras desen by Andrew D. Cherniack, Jes K. Klarlund et al."Disassembly of Son-of-sevenless proteins from Grb2 during p21ras desen" by Andrew D. Cherniack, Jes K. Klarlund et al.

... apparently by mobilizing complexes of Grb2 and the guanine nucleotide exchangers Son-of-sevenless (Sos) 1 and 2 to associate ... with tyrosine-phosphorylated proteins in the plasma membrane. Here we show that in 32P-labeled 3T3-L1 adipocytes the elevated ... cellular concentrations of [32P]GTP-bound p21ras in response to insulin return to near basal levels after 20-30 min of hormone ... These data are consistent with the hypothesis that the dissociation of Grb2 from Sos proteins caused by insulin in 3T3-L1 cells ...
more infohttps://escholarship.umassmed.edu/oapubs/813/

IJMS  | Free Full-Text | MAPKs and Signal Transduction in the Control of Gastrointestinal Epithelial Cell Proliferation and...IJMS | Free Full-Text | MAPKs and Signal Transduction in the Control of Gastrointestinal Epithelial Cell Proliferation and...

Mitogen-activated protein kinase (MAPK) pathways are activated by several stimuli and transduce the signal inside cells, ... a protein that contains Src homology 2 (SH2) domains, which are cytosolic and bound to Son of Sevenless (SOS). SOS is a guanine ... Receptor tyrosine kinases activate canonical WNT/β-catenin signaling via MAP kinase/LRP6 pathway and direct β-catenin ... The maintenance of signaling efficiency still depends on scaffold proteins that selectively bind to the multiple components, ...
more infohttp://www.mdpi.com/1422-0067/14/5/10143/htm

IJMS  | Free Full-Text | Functions and Mechanisms of Fibroblast Growth Factor (FGF) Signalling in Drosophila melanogaster | HTMLIJMS | Free Full-Text | Functions and Mechanisms of Fibroblast Growth Factor (FGF) Signalling in Drosophila melanogaster | HTML

In the genetic model Drosophila melanogaster, FGF signalling via the receptor tyrosine kinases Heartless (Htl) and Breathless ( ... which recruits the guanine nucleotide exchange factor, Son of sevenless (Sos) to activate the small GTPase Ras85D [63] (Figure ... Tyrosine residues that are indicated in binding of downstream signalling molecules are marked (red). The Tyrosine residue ... and trans-phosphorylation of their tyrosine kinase domains and to phosphorylation of its adaptor protein Dof. Dof protein is O- ...
more infohttps://www.mdpi.com/1422-0067/14/3/5920/htm

Resistance to Trastuzumab in Breast Cancer | Clinical Cancer ResearchResistance to Trastuzumab in Breast Cancer | Clinical Cancer Research

GRB2 binds to the guanine nucleotide exchange factor Son of Sevenless (SOS) by one of its SH3 domains. When the GRB2/SOS ... is an adaptor protein that contains one Src Homology 2 (SH2) domain, which recognizes the tyrosine-phosphorylated sites on the ... Recombinant human insulin-like growth factor binding protein 3 inhibits growth of human epidermal growth factor receptor-2- ... The Fab contains the antigen-binding sites of the antibody, whereas the Fc contains the binding sites for Fc receptors present ...
more infohttp://clincancerres.aacrjournals.org/content/15/24/7479.full

Brain Metastases: The HER2 Paradigm | Clinical Cancer ResearchBrain Metastases: The HER2 Paradigm | Clinical Cancer Research

... son-of-sevenless guanine nucleotide exchange factor. ... growth factor receptor-bound protein 2; GSK-3, glycogen kinase ... Ligand binding induces dimerization, leading to activation of the intracellular tyrosine kinase. On auto- and cross- ... Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 1985; ... The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science 1986;232:1644-6. ...
more infohttps://clincancerres.aacrjournals.org/content/13/6/1648?ijkey=5852052144eb9d8357f5f1bc0d510cc20872d4e2&keytype2=tf_ipsecsha

Cancers  | Free Full-Text | Genetic Interactions of STAT3 and Anticancer  Drug Development | HTMLCancers | Free Full-Text | Genetic Interactions of STAT3 and Anticancer Drug Development | HTML

As members of a subfamily of small guanine nucleotide-binding proteins, Ras proteins (HRAS, KRAS, and NRAS) cycle between ... Activation of EGFR results in the assembly of Grb2 and the Son of Sevenless (SOS) complex; SOS is one of the guanine nucleotide ... binds to Y1148 and Y1173 in EGFR [190,201], whereas phospholipase Cγ binds to Y992 [202] and the protein tyrosine phosphatase ... proteins [116,117] or cytokine-induced SH2 protein [118] provides negative feedback for JAK/STAT activation. SOCS proteins bind ...
more infohttp://mdpi.com/2072-6694/6/1/494/htm

An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro.  - PubMed - NCBIAn SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro. - PubMed - NCBI

... and that this protein can bind in vitro to sevenless and to Son of sevenless (Sos), a putative guanine nucleotide exchange ... Activation of the sevenless protein-tyrosine kinase is required for the proper specification of R7 photoreceptors in the ... An SH3-SH2-SH3 protein is required for p21Ras1 activation and binds to sevenless and Sos proteins in vitro.. Simon MA1, Dodson ... Here we report that another gene, E(sev)2B, required for proper signaling by sevenless encodes a protein of the structure SH3- ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/8462097?dopt=Abstract

Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis | European Respiratory SocietyMode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis | European Respiratory Society

... protein kinase C; PLC-γ: phospholipase C-γ; SOS: son of sevenless, a guanine nucleotide exchange factor that acts on the Ras ... Nintedanib blocks kinase activity by occupying the intracellular ATP-binding pocket of specific tyrosine kinases. The binding ... growth factor receptor-bound protein 2; MEK1/2: mitogen-activated protein kinase kinase 1/2; PDGF: platelet-derived growth ... Nintedanib binds to the intracellular ATP binding pocket of fibroblast growth factor receptors (FGFRs), platelet-derived growth ...
more infohttps://erj.ersjournals.com/content/45/5/1434?ijkey=9536cd74cb6405690efb246de9906d463c2b46d6&keytype2=tf_ipsecsha

SMART: RasGEF domain annotationSMART: RasGEF domain annotation

Binding / catalysis: protein-binding, Ras-binding, guanine nucleotide exchange activity towards Ras ... Son of sevenless (gene sos) from Drosophila and mammals.. * p140-RAS GRF (cdc25Mm) from mammals. This protein possesses both a ... Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling. ... protein-protein or protein-nucleotide interactions. GTP-binding proteins are no exception to the rule. They regulate cellular ...
more infohttp://smart.embl-heidelberg.de/smart/do_annotation.pl?BLAST=DUMMY&DOMAIN=RasGEF

SMART: RasGEF domain annotationSMART: RasGEF domain annotation

Binding / catalysis: protein-binding, Ras-binding, guanine nucleotide exchange activity towards Ras ... Son of sevenless (gene sos) from Drosophila and mammals.. * p140-RAS GRF (cdc25Mm) from mammals. This protein possesses both a ... Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling. ... protein-protein or protein-nucleotide interactions. GTP-binding proteins are no exception to the rule. They regulate cellular ...
more infohttp://smart.embl-heidelberg.de/smart/do_annotation.pl?DOMAIN=RasGEF&BLAST=DUMMY

SMART: RasGEFN domain annotationSMART: RasGEFN domain annotation

... or GTP-bound form suggests that CDC25 catalyzes exchange of guanine nucleotides bound to Ras proteins by stabilization of the ... Experimentally Phased Structure of Human the Son of Sevenless protein at 4.1 Ang. ... Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling. ... we developed a protein-protein binding assay. We determined that CDC25 binds tightly to Ras2 protein only in the absence of ...
more infohttp://smart.embl.de/smart/do_annotation.pl?DOMAIN=RasGEFN&START=300&END=434&E_VALUE=3.12e-34&TYPE=SMART&BLAST=DARYVVVSGTPEKILEHLLNDLHLAEVQHKETETLLDDFLLTYTVFMTTDDLCQALLRHYSAKKYQGEEENSDVPCRKRKVLHLVSQWISLYKDWLHEDEHSKMFLKTIYRNVLDDVYEYPILEKELKEFQKILG

SMART: RasGEFN domain annotationSMART: RasGEFN domain annotation

... or GTP-bound form suggests that CDC25 catalyzes exchange of guanine nucleotides bound to Ras proteins by stabilization of the ... Experimentally Phased Structure of Human the Son of Sevenless protein at 4.1 Ang. ... Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling. ... we developed a protein-protein binding assay. We determined that CDC25 binds tightly to Ras2 protein only in the absence of ...
more infohttp://smart.embl.de/smart/do_annotation.pl?DOMAIN=RasGEFN&START=65&END=184&E_VALUE=3.19e-8&TYPE=SMART&BLAST=

Specific inhibitors of the protein tyrosine phosphatase Shp2 identified by high-throughput docking | PNASSpecific inhibitors of the protein tyrosine phosphatase Shp2 identified by high-throughput docking | PNAS

... and the Ras guanine nucleotide exchange factor Son of Sevenless (Sos) (55). Furthermore, PHPS1 has no effect on the Shp2- ... the multiadaptor protein Gab1 (15), Csk-binding protein [Cbp/PAG (16)], and paxillin (17). Downstream of the hepatocyte growth ... 1995) Protein-tyrosine-phosphatase SHPTP2 is a required positive effector for insulin downstream signaling. Proc Natl Acad Sci ... The protein tyrosine phosphatase Shp2 is a positive regulator of growth factor signaling. Gain-of-function mutations in several ...
more infohttps://www.pnas.org/content/105/20/7275?ijkey=375b47c0343f45ffb093be33baaf38de860b3ace&keytype2=tf_ipsecsha

Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2 | ScienceHuman Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2 | Science

... the product of the Drosophila son of sevenless gene. The hSos1 protein contains a region of significant sequence similarity to ... These results suggest that the coupling of receptor tyrosine kinases to Ras signaling is mediated by a molecular complex ... Thus hSos1 is a guanine nucleotide exchange factor for Ras. The hSos1 interacted with growth factor receptor-bound protein 2 ( ... Human Sos1: a guanine nucleotide exchange factor for Ras that binds to GRB2 ...
more infohttps://science.sciencemag.org/content/260/5112/1338

CACHE . The Effects of Nerve Growth Factor on the Growth and Survival of the A875 Human Melanoma Cell Line . Kalamazoo CollegeCACHE . The Effects of Nerve Growth Factor on the Growth and Survival of the A875 Human Melanoma Cell Line . Kalamazoo College

GRB2 is an adapter protein, linking tyrosine kinase receptors to guanine nucleotide-releasing factor, Son of sevenless ... ... Growth factor receptor-binding protein-2 (GRB2) is a key molecule in growth factor signal transduction. ... Epidermal Growth Factor Induces Phosphorylation on Growth Factor Receptor-Binding Protein-2 (GRB2) in A431 Epidermal Carcinoma ... Nerve growth factor (NGF) is a classical example of a protein that promotes survival, neurite extension, and transmitter ...
more infohttps://cache.kzoo.edu/handle/10920/23194

G Proteins in Cancer: The Prostate Cancer Paradigm | Science SignalingG Proteins in Cancer: The Prostate Cancer Paradigm | Science Signaling

... including Grb2 and its associated Ras guanine exchange factor son of sevenless (SOS), to the plasma membrane. Recruitment of ... and c-Src family nonreceptor tyrosine kinases may be early intermediates in the pathway (Fig. 4). Free Gβγ can directly bind ... and subsequent binding of β-arrestin proteins (26, 49). Binding of β-arrestin proteins to receptors uncouples the receptor from ... Activation cycle of heterotrimeric G proteins. An agonist-bound receptor catalytically activates the G protein, leading to ...
more infohttps://stke.sciencemag.org/content/2004/216/re2?ijkey=988baedbfd16eac70122e88014ff10a64c0ebeca&keytype2=tf_ipsecsha

VEGF Family Ligands and Receptor Interactions | Thermo Fisher Scientific - ARVEGF Family Ligands and Receptor Interactions | Thermo Fisher Scientific - AR

Explore the VEG family ligands and receptor interactions and find antibodies to detect some of the target proteins in the ... Growth Factor Receptor-Bound Protein-2); SOS (Son of Sevenless); and the Src homology domain containing SHC proteins. ... association of the adaptor protein GRB2 to the receptor and subsequent stimulation of the guanine-nucleotide exchange protein ... downstream of most protein tyrosine kinase receptors including activation of the transcription factor, c-Fos [4]. Moreover, ...
more infohttp://www.thermofisher.com/ar/es/home/life-science/antibodies/antibodies-learning-center/antibodies-resource-library/cell-signaling-pathways/vegf-family-ligands-receptor-interactions.html

Insulin regulation of the Ras activation/inactivation cycle | SpringerLinkInsulin regulation of the Ras activation/inactivation cycle | SpringerLink

Ras l and a putative guanine nucleotide exchange factor perform crucial steps in signalling by the sevenless proteins tyrosine ... Cherniack AD, Klarlund JK, Conway BR, Czech MP: Disassembly of son-of-sevenless proteins from Grb2 during p21 Ras ... Many of these mitogenic responses are mediated by signals through the small molecular weight guanine nucleotide binding protein ... Guanine-nucleotide-releasing factor hSos1 binds to Grb2 and links receptor tyrosine kinases to Ras signalling. Nature 363: 85- ...
more infohttps://link.springer.com/article/10.1023%2FA%3A1006819008507

Michael A. Simon - Searle Scholars ProgramMichael A. Simon - Searle Scholars Program

... protein. The third, downsteam of receptor kinases (drk) encodes a protein that binds to the sevenless and Sos proteins. These ... The other, Son of sevenless (Sos), encodes a putative guanine nucleotide exchange factor that may function to stimulate the ... The sevenless locus encodes a transmembrane receptor molecule that contains an intracellular protein tyrosine kinase domain. ... The activation of sevenless kinase activity in response to the binding of its ligand, the product of the bride of sevenless ...
more infohttps://www.searlescholars.net/people/michael-a-simon

Plus itPlus it

Raf kinase inhibitor protein; SOS, son of sevenless; TF, transcription factors; TK, tyrosine kinase. ... the guanine-nucleotide exchange factor Sos potentiates Ras, by catalyzing the replacement of GDP for GTP. GTP-bound Ras ... Jun-Jun and Jun-Fos protein complexes). Following homodimerization/heterodimerization, AP-1 proteins bind to the so-called TREs ... GTP-bound Ras interacts with Raf and mobilizes the inactive protein from the cytoplasm. Once the Ras-Raf complex is ...
more infohttp://mct.aacrjournals.org/content/6/3/811

Development - Beta-adrenergic receptors regulation of ERK Pathway Map - PrimePCR | Life Science | Bio-RadDevelopment - Beta-adrenergic receptors regulation of ERK Pathway Map - PrimePCR | Life Science | Bio-Rad

... and Growth factor receptor-bound protein 2 (GRB2), activating Son of sevenless homolog (SOS)/ H-Ras/ c-Raf-1 and subsequent MEK ... G-protein alpha-i family activation releases complex of G-protein beta/gamma, which activates c-src tyrosine kinase (c-Src) [12 ... Direct binding of the beta1 adrenergic receptor to the cyclic AMP-dependent guanine nucleotide exchange factor CNrasGEF leads ... PKA-cat phosphorylation of Beta-2 adrenergic receptor leads to its activation switch from G-protein alpha-i family to G-protein ...
more infohttp://www.bio-rad.com/en-us/prime-pcr-assays/pathway/cardiac-hypertrophy/development-beta-adrenergic-receptors-regulation-erk

Signaling Networks in Biology - CHEMICAL BIOLOGYSignaling Networks in Biology - CHEMICAL BIOLOGY

... a receptor tyrosine kinase) and Sos (Son-of-Sevenless, a guanine nuclear exchange factor, GEF) that in turn regulates Ras (R- ... Binding interactions typically occur between two or more proteins, proteins and lipids, or proteins and small molecules. ... Analysis of sequence specificities of DNA-binding proteins with protein binding microarrays. Methods Enzymol. 2006; 410:279-299 ... recruiting adaptor proteins Gab1 (growth factor receptor bound protein 2-associated protein 1). Gab1 is phosphorylated by EGFR ...
more infohttp://schoolbag.info/chemistry/chemical_biology/195.html

The Ras guanine nucleotide exchange factor RasGRF1 promotes matrix metalloproteinase-3 production in rheumatoid arthritis...The Ras guanine nucleotide exchange factor RasGRF1 promotes matrix metalloproteinase-3 production in rheumatoid arthritis...

Double staining was performed to detect proteins in specific cell populations, and cells producing MMP-1 and MMP-3. RasGRF1 ... Recently, expression and post-translational modification of Ras guanine nucleotide releasing factor 1 (RasGRF1) was found to ... such as Son-of-sevenless coupling to tyrosine kinase-dependent receptors, and Ras guanine nucleotide-releasing factor 1 (RasGRF ... The binding of GTP to Ras superfamily GTPases leads to a conformational change in the GTPase, allowing signaling to downstream ...
more infohttps://arthritis-research.biomedcentral.com/articles/10.1186/ar2785

The 70 kDa S6 kinase : enrichment and characterization of sea star homologue, and the role of p70S6K in the transformed...The 70 kDa S6 kinase : enrichment and characterization of sea star homologue, and the role of p70S6K in the transformed...

These receptors utilize small guanine nucleotide-binding (G) proteins, cytoplasmic serine/threonine or tyrosine protein 5 ... 1). A proline-rich region of the guanine nucleotide exchange protein Son-of sevenless (SOS) associates with the SH3 domains of ... A column that did not bind the protein of interest but did bind other contaminating proteins could be used as a negative column ... One of the proteins that binds to activated receptor tyrosine kinases is the SH2 domain-containing adaptor protein Grb-2 ( ...
more infohttps://open.library.ubc.ca/cIRcle/collections/ubctheses/831/items/1.0089131
  • Lysates of such desensitized cells were quantitatively immunoprecipitated with an antiserum recognizing both Sos1 and Sos2 proteins or a specific anti-Sos2 antiserum. (umassmed.edu)
  • Immunoblot analysis of these precipitates revealed that insulin causes a marked hyperphosphorylation of Sos1 and a 50% decrease in Grb2 associated with Sos proteins under these conditions. (umassmed.edu)
  • Similarly, anti-Grb2 immunoprecipitates of such lysates revealed the presence of decreased Sos1 protein due to insulin action. (umassmed.edu)
  • Here we show that in 32P-labeled 3T3-L1 adipocytes the elevated cellular concentrations of [32P]GTP-bound p21ras in response to insulin return to near basal levels after 20-30 min of hormone stimulation, while insulin receptors remain activated. (umassmed.edu)
  • Mitogen-activated protein kinase (MAPK) pathways are activated by several stimuli and transduce the signal inside cells, generating diverse responses including cell proliferation, differentiation, migration and apoptosis. (mdpi.com)
  • Although the pathogenic pathways involved in IPF have not been fully elucidated, IPF is believed to be caused by repetitive alveolar epithelial cell injury and dysregulated repair, in which there is uncontrolled proliferation of lung fibroblasts and differentiation of fibroblasts into myofibroblasts, which excessively deposit extracellular matrix (ECM) proteins in the interstitial space. (ersjournals.com)
  • The nature of intracellular signaling pathways mediating mitogenic effects of GPCRs in prostate cancer is poorly defined, although the G protein-dependent activation of the Ras-to-mitogen-activated protein kinase pathway has emerged as a critical regulatory event. (sciencemag.org)
  • Lysates of such desensitized cells were quantitatively immunoprecipitated with an antiserum recognizing both Sos1 and Sos2 proteins or a specific anti-Sos2 antiserum. (umassmed.edu)
  • Ras-mediated activation of DH-PH-Sos did not require activation of mitogen-activated protein kinase but it was dependent on activation of phosphoinositide 3-kinase. (embl-heidelberg.de)
  • Growing evidence suggests that the Ras/mitogen-activated protein kinase (MAPK) signaling cascade represents a pivotal molecular circuitry participating directly or indirectly in prostate cancer evolution. (aacrjournals.org)
  • The Ras/mitogen-activated protein kinase (MAPK) signaling pathway has long been identified as a convergence point for numerous (normal and pathologic) signaling inputs, rendering it an appealing target for therapeutic intervention ( 4 ). (aacrjournals.org)
  • PKA-cat activates RAP1A member of RAS oncogene family ( RAP-1A )/ v-raf murine sarcoma viral oncogene homolog B1 ( B-Raf )/ Mitogen-activated protein kinase kinase 2 and 1 ( MEK2(MAP2K2) and MEK1(MAP2K1) )/ Erk [ 6 ]. (bio-rad.com)
  • They regulate cellular processes as diverse as protein biosynthesis and intracellular membrane trafficking. (embl-heidelberg.de)
  • The best-studied effectors are phosphoinositide 3′ kinase (PI3K), Ral guanine nucleotide dissociation stimulator (RalGDS), and RAF ( 8 , 20 , 35 ). (asm.org)
  • These states are regulated by the balance between the intrinsic GTPase activity of the proteins: their interactions with inhibitory proteins and with activating proteins that regulate the exchange of GDP for GTP. (aacrjournals.org)
  • Thus, upon binding to GTP, the duration of Ras-GTPase activity depends on the rate of hydrolysis. (wikipedia.org)
  • Once released from SOS, the Ras-GTPase quickly binds fresh guanine nucleotide from the cytosol. (wikipedia.org)
  • The normal rate of Ras catalytic GTPase (GTP hydrolysis) activity can be increased by proteins of the RasGAP family, which bind to Ras and increase its catalytic rate by a factor of one thousand - in effect, increasing the rate at which Ras is inactivated. (wikipedia.org)
  • This may be explained because the SOS1 protein adopts an auto-inhibited conformation dependent on multiple domain-to-domain interactions that cooperate to block access of the SOS1 catalytic core to its Ras-GTPase targets. (wikipedia.org)
  • We have identified the phenylhydrazonopyrazolone sulfonate PHPS1 as a potent and cell-permeable inhibitor, which is specific for Shp2 over the closely related tyrosine phosphatases Shp1 and PTP1B. (pnas.org)
  • SH2 domain‐containing proteins in this group are tightly associated with catalytic molecules, and function as adaptors linking these molecules to phosphotyrosine‐containing proteins. (embopress.org)
  • In the last decade, great progress has been made in understanding the molecular mechanisms which regulate the insulin mediated conversion of Ras from its inactive, GDP-bound state, to the activated GTP-bound form. (springer.com)
  • The activation of sevenless kinase activity in response to the binding of its ligand, the product of the bride of sevenless locus, is crucial for the proper development of a single cell within each unit of the compound eye. (searlescholars.net)
  • The naturally occurring ligands that have an affinity for EGFR are EGF, transforming growth factor (TGF-α), and β-cellulin (8), all of which are small proteins, whereas the natural ligand for TLR is a macromolecule, lipopolysaccharide (LPS). (schoolbag.info)
  • The deregulation of Shc proteins has been linked to different disease conditions, including cancer and Alzheimer's, which indicates their key roles in cellular functions. (jmolecularsignaling.com)
  • In the absence of sevenless activity, a precursor cell that would normally differentiate as the R7 photoreceptor instead becomes a non-neuronal lens-secreting cell. (searlescholars.net)
  • For example, EGF is generated by the proteolytic cleavage of the membrane-bound precursor, heparin-binding EGF-like factor (HB-EGF), by a matrix metalloproteinase (MMP) (9). (schoolbag.info)
  • Phosphorylated PLC-Gamma catalyzes the hydrolysis of PIP2 to generate IP3 (Inositol-1,4,5-trisphosphate) and DAG (Diacylglycerol), which are known to stimulate the release of Ca 2+ (Calcium) from internal stores and activate PKC (Protein Kinase-C), respectively. (thermofisher.com)
  • These results have suggested that an important action of the sevenless protein may be to stimulate the activity of the Ras1 protein. (searlescholars.net)
  • Recently, expression and post-translational modification of Ras guanine nucleotide releasing factor 1 (RasGRF1) was found to contribute to spontaneous MMP production in melanoma cancer cells. (biomedcentral.com)
  • Downward J: Regulatory mechanisms for Ras proteins. (springer.com)
  • This activates Protein kinase cAMP-dependent regulatory ( PKA-reg (cAMP-dependent) and catalytic ( PKA-cat (cAMP-dependent) ) subunits. (bio-rad.com)
  • MEKK1 and NIK also associate in cells and this interaction is mediated by regulatory domains on both proteins. (embopress.org)
  • Empty Ras subsequently binds to GTP, available at excess levels in the cell ( 8 , 20 ). (asm.org)
  • Nerve growth factor (NGF) is a classical example of a protein that promotes survival, neurite extension, and transmitter production in neurons. (kzoo.edu)
  • Importantly, inhibition of G protein signaling attenuates prostate cancer cell growth in animal models. (sciencemag.org)
  • Recently, a large number of genes encoding GTP-binding proteins and the proteins that interact with these molecular switches have been cloned and expressed. (embl-heidelberg.de)
  • Currently it is estimated that the human genome contains 25,000 protein-encoding genes (1), which correspond to several hundred thousand possible protein species resulting from alternative splicing and posttranslational modifications. (schoolbag.info)