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 2.7.10.1) - 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 2.7.10.1) 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 2.7.10.1) 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 2.7.10.1) - 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 ...