Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TYROSINE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 559 records · Page 31Linked to original sources
PubMed1994

p59fyn tyrosine kinase regulates p56lck tyrosine kinase activity and early TCR-mediated signaling.

To study the role of p59fyn in T cell activation, we used antisense RNA to inhibit p59fyn expression in a T cell clone. Transfectants with reduced levels of p59fyn were functionally impaired in their responses to antigen, Con A+recombinant IL-1 and cross-linking with anti-TCR mAb. Induction of tyrosine phosphorylation on most intracellular substrates was greatly reduced. We also noted that the lck kinase activity was greatly reduced even though the amount of lck protein was equivalent to that present in parental D10 cells. Our results suggest that the protein tyrosine kinase p59fyn is critical in TCR-mediated signaling and also suggests that p59fyn may regulate p56lck tyrosine kinase activity.

Animals↗
PubMed1991

Phosphorylation of c-Src on tyrosine 527 by another protein tyrosine kinase.

The protein tyrosine kinase activity of the cellular Src protein is negatively regulated by phosphorylation at tyrosine residue 527 (Tyr527). It has not been established whether this regulatory modification of Src is mediated by autophosphorylation or by another cellular protein kinase. The phosphorylation of a modified form of c-Src that lacks kinase activity was examined in mouse cells that do not express endogenous Src (because of the targeted disruption of both src alleles). Phosphorylation of the inactive form of Src on Tyr527 occurred to a similar extent in cells lacking endogenous Src as it did in cells expressing Src. Therefore, Tyr527 phosphorylation, and thus negative control of Src kinase activity, is mediated by another cellular protein tyrosine kinase.

Amino Acid Sequence↗
PubMed1994

The role of protein tyrosine kinases and protein tyrosine phosphatases in T cell antigen receptor signal transduction.

Engagement of the T cell antigen receptor (TCR) by peptide antigen bound to the major histocompatibility complex (MHC) molecules initiates a biochemical cascade involving protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPases). Recent biochemical and genetic evidence has implicated at least three cytoplasmic protein tyrosine kinases (PTKs), Lck, Fyn, and ZAP-70, that are involved in the initiation of TCR signal transduction. In addition, genetic evidence has demonstrated the requirement of the transmembrane PTPase, CD45, for TCR function. Activation of T cells through the TCR represents an alteration in the dynamic equilibrium between PTKs and PTPases. The TCR is a multi-subunit complex composed of at least six different gene products. Dissection of the TCR utilizing chimeric receptors and TCR mutants has demonstrated that the multi-subunit receptor is composed of at least two signal transducing modules, the CD3 and the zeta chain subunits. These two modules have in common peptide sequences within their cytoplasmic domains termed antigen recognition activation motifs (ARAMs) that are responsible for transducing signaling events. Moreover, the ARAM sequence is also found in subunits associated with a variety of other hematopoietic cell antigen receptors and is likely to form the basis for interactions with effector molecules within the signaling cascades of these receptors. Here we review the mechanism by which the ARAM sequences interact with PTKs and the cascades of PTKs and PTPases that are involved in mediating TCR function.

Amino Acid Sequence↗
PubMed2001

Deoxygenation of sickle cells stimulates Syk tyrosine kinase and inhibits a membrane tyrosine phosphatase.

Polymerization of hemoglobin S in sickle red cells, in deoxygenated conditions, is associated with K+ loss and cellular dehydration. It was previously reported that deoxygenation of sickle cells increases protein tyrosine kinase (PTK) activity and band 3 tyrosine phosphorylation and that PTK inhibitors reduce cell dehydration. Here, the study investigates which PTKs are involved and the mechanism of their activation. Deoxygenation of sickle cells induced a 2-fold increase in Syk activity, measured by autophosphorylation in immune complex assays, but had no effect on Lyn. Syk was not stimulated by deoxygenation of normal red cells, and stimulation was partly reversible on reoxygenation of sickle cells. Syk activation was independent of the increase in intracellular Ca++ and Mg2+ associated with deoxygenation. Lectins that promote glycophorin or band 3 aggregation did not activate Syk. In parallel to Syk stimulation, deoxygenation of sickle cells, but not of normal red cells, decreased the activity of both membrane-associated protein tyrosine phosphatase (PTPs) and membrane protein thiol content. In vitro pretreatment of Syk immune complexes with membrane PTP inhibited Syk autophosphorylation. It is suggested that Syk activation in vivo could be mediated by PTP inhibition, itself resulting from thiol oxidation, as PTPs are known to be inhibited by oxidants. Altogether these data indicate that Syk could be involved in the mechanisms leading to sickle cell dehydration.

Anemia, Sickle Cell↗
PubMedDate not supplied

The catalytic mechanism of tyrosine phenol-lyase from Erwinia herbicola: the effect of substrate structure on pH-dependence of kinetic parameters in the reactions with ring-substituted tyrosines.

Apparently homogeneous tyrosine phenol-lyase (TPL) from Erwinia herbicola has been prepared by a new method. The pH-dependencies of the main kinetic parameters for the reactions of Erwinia TPL with tyrosine, 2-fluorotyrosine, 3-fluorotyrosine, 2-chlorotyrosine, and 3,4-dihydroxyphenylalanine (DOPA) have been studied. The pattern of pH-dependence of V(max) depends on the nature of the substituent in the aromatic ring. For the substrates bearing small substituents (H, 2-F, 3-F) V(max) values were found to be pH-independent. For 2-chlorotyrosine and DOPA V(max) decreased at lower pH, the effect being described by equation with one pKa. Generally two bases are reflected in the pH dependence of V(max)/Km. The first base, probably is responsible for the abstraction of alpha-proton, while the second one, interacts with the phenolic hydroxyl at the stage of binding. The reaction of TPL with DOPA differs from the reactions with other tyrosines by the requirement of an additional base which is reflected in the pH-profiles of both V(max) and V(max)/Km. For the reaction of TPL from Citrobacter intermedius with DOPA only V(max)/Km values could be determined. The activity of Citrobacter enzyme towards DOPA is considerably less than that of E. herbicola enzyme, and its maximal value is attained at higher pH.

Ammonium Sulfate↗
PubMed2002

TCR engagement induces proline-rich tyrosine kinase-2 (Pyk2) translocation to the T cell-APC interface independently of Pyk2 activity and in an immunoreceptor tyrosine-based activation motif-mediated fashion.

The relocation of kinases in T lymphocytes during their cognate interaction with APCs is essential for lymphocyte activation. We found that the proline-rich tyrosine kinase-2 (Pyk2) is rapidly translocated to the T cell-APC contact area upon T cell-specific recognition of superantigen-pulsed APCs. Stimulation with anti-CD3-coated latex microspheres was sufficient for Pyk2 reorientation, and the coengagement of CD28 boosted Pyk2 redistribution. Nevertheless, Pyk2 translocation did not result in its recruitment to lipid rafts. Two results support that Pyk2 translocation was independent of its kinase activity. First, Lck activity was required for TCR-induced Pyk2 translocation, but not for TCR-induced Pyk2 activation. Second, a kinase-dead Pyk2 mutant was equally translocated upon TCR triggering. In addition, Lck activity alone was insufficient to induce Pyk2 reorientation and activation, requiring the presence of at least one intact immunoreceptor tyrosine-based activation motif (ITAM). Despite the dependence on functional Lck and on phosphorylated ITAM for Pyk2 translocation, the ITAM-binding tyrosine kinase zeta-associated protein 70 (ZAP-70) was not essential. All these data suggest that, by translocating to the vicinity of the immune synapse, Pyk2 could play an essential role in T cell activation and polarized secretion of cytokines.

Amino Acid Motifs↗
PubMed1976

[Induction of tyrosine aminotransferase by blastomogenic metabolites of tryptophan and tyrosine].

A comparitive study was made of the effect produced by endogenous blastomogenic agents (3-oxyanthranylic and paraoxphenyl-lactic acids) and their nonblastomogenic anaogues (anthranylic and phenyl-lactic acids) on the activity of tyrosine-aminotranspherase in the rat liver. Blastomogenic metabolites proved to be capable of inducing sharply the enzyme activity. This phenomenon and data on the role played by the increase in the activity of tyrosine-aminotranspherase and tryptophane-oxygenase in tyrosine and tryptophane catabolism on the way of a possible formation of blastomogenic metabolites permitted to put forward a suggestion on the "chain reaction" of accumulation of the endogenous blastomogenic agents in the organism.

3-Hydroxyanthranilic Acid↗
PubMed2000

Changes and mechanisms of protein-tyrosine kinase and protein-tyrosine phosphatase activities after brain ischemia/reperfusion.

AIM: To study the changes and mechanisms of protein-tyrosine kinase (PTK) and protein-tyrosine phosphatase (PTP) activities in the hippocamal synaptosome following cerebral ischemia/reperfusion (I/R) in gerbil. METHODS: Transient (15 min) global ischemia was produced by bilateral carotid artery occlusion. Total PTK and PTP activities were measured by [r-32P] incorporation and colorimetric analysis, respectively. Src and proline-rich tyrosine kinase2 (PYK2) activities were measured by immunoprecipitation and [r-32P] incorporation. RESULTS: Total PTK activity increased significantly after I/R, but the PTP activity did not change. The Src activity was much higher than PYK2 activity in sham-operated controls. I/R mainly caused a pronounced increase in Src activity, but not PYK2 activity. The increase in Src activity had no relation to the expression of Src protein. Administration of ketamine (KT) or nifedipine (ND) 20 min before ischemia caused a decrease in total PTK and Src activities, and no change in the PYK2 and PTP activities. CONCLUSION: The increase in PTK activity caused by I/R may be mainly due to the increase in Src activity. This increase in Src activity has no relation to the expression of Src protein. But it is related to the activation of NMDA (N-methyl-D-aspartate) receptor (NR) and L-type voltage-gated calcium channel (L-type VGCC). In other words, the increase in total PTK and Src activities induced by I/R may be mediated via NR and L-type VGCC. The PTP activity did not change during I/R.

Animals↗
PubMed1992

Protein tyrosine phosphatase-1C is rapidly phosphorylated in tyrosine in macrophages in response to colony stimulating factor-1.

An approximately 64-kDa cytoplasmic protein is rapidly phosphorylated in tyrosine in the response of macrophages to colony stimulating factor-1. To identify this protein, BAC1.2F5 macrophages were incubated with or without colony stimulating factor-1, the phosphotyrosine-containing portion of their cytosolic fractions subjected to size exclusion chromatography, and the 45-70-kDa fraction further fractionated by reverse phase high pressure liquid chromatography (RP-HPLC). Tryptic peptides of pooled RP-HPLC fractions from stimulated cells (containing the approximately 64-kDa protein and an approximately 54-kDa protein) and from unstimulated cells (containing the approximately 54-kDa protein alone), were sequenced directly. All seven readable sequences of 8 sequenceable peptides present uniquely in the stimulated fraction were present in the sequence of the src homology 2 domain-containing protein tyrosine phosphatase-1C (PTP-1C). The identity of the approximately 64-kDa protein was confirmed by Western blotting with an antibody raised to a PTP-1C peptide. The rapid, growth factor-induced tyrosine phosphorylation of PTP-1C suggests that it may be involved in very early events in growth factor signal transduction.

Amino Acid Sequence↗
PubMed1984

Tyrosine phosphorylation of the insulin receptor beta subunit activates the receptor-associated tyrosine kinase activity.

The regulation of kinase activity associated with insulin receptor by phosphorylation and dephosphorylation has been examined using partially purified receptor immobilized on insulin-agarose. The immobilized receptor preparation exhibits predominately tyrosine but also serine and threonine kinase activities toward insulin receptor beta subunit and exogenous histone. Phosphorylation of the insulin receptor preparation with increasing concentrations of unlabeled ATP, followed by washing to remove the unreacted ATP, results in a progressive activation of the receptor kinase activity when assayed in the presence of histone and [gamma-32P]ATP. A maximal 4-fold activation is achieved by prior incubation of receptor with concentrations of ATP approaching 1 mM. High pressure liquid chromatographic analysis of tryptic hydrolysates of the 32P-labeled insulin receptor beta subunit reveals three domains of phosphorylation (designated peaks 1, 2, and 3). Phosphotyrosine and phosphoserine residues are present in these three domains while peak 2 contains phosphothreonine as well. Thus, at least seven sites are available for phosphorylation on the beta subunit of the insulin receptor. Incubation of the phosphorylated insulin receptor with alkaline phosphatase at 15 degrees C results in the selective dephosphorylation of the phosphotyrosine residues on the beta subunit of the receptor while the phosphoserine and phosphothreonine contents are not affected. The dephosphorylation of the receptor is accompanied by a marked 65% inhibition of the receptor kinase activity. Almost 90% of the decrease in [32P]phosphate content of the receptor after alkaline phosphatase treatment is accounted for by a decrease in phosphotyrosine content in peak 2, while very small decreases are observed in peaks 1 and 3, respectively. These results demonstrate that the extent of phosphorylation of tyrosine residues in receptor domain 2 closely parallels the receptor kinase activity state, suggesting phosphorylation of this domain may play a key role in regulating the insulin receptor tyrosine kinase.

Amino Acids↗
PubMed1994

Modulation of the cytotoxic activity of tumor necrosis factor by protein tyrosine kinase and protein tyrosine phosphatase inhibitors.

The mechanism by which tumor necrosis factor (TNF) inhibits cell growth is not known. The importance of tyrosine phosphorylation in mediating the cytotoxicity of TNF has been suggested from previous studies. In this report, we investigated the effects of both tyrosine kinase (TK) and protein tyrosine phosphatase (PTP) inhibitors on the cytotoxic effects of TNF. TNF-induced changes in cellular PTPase activity were also examined. Incubation of tumor cells with genistein or tyrphostin, known TK inhibitors, protected against TNF cytotoxicity in a dose-dependent manner. Protection by TK inhibitors was observed at early time points after the start of TNF incubation. Preincubation of tumor cells with sodium orthovanadate, a known PTPase inhibitor, also protected against TNF cytotoxicity only at early time points after addition of TNF. Activation of total cellular PTPase activity by TNF was observed at early times of TNF incubation only in TNF-sensitive cell lines. Immunoblot analysis revealed that TNF enhanced tyrosyl phosphorylation of the epidermal growth factor receptor (EGFR) only in TNF-sensitive cell lines. No other substrates were tyr-phosphorylated after addition of TNF. The results suggest that both cellular PTKs and PTPases play a significant role in orchestrating the early events in the cytotoxic response of TNF. The nature and types of PTKs and PTPases involved in this process need further investigation.

Catechols↗
PubMed1994

Prolactin-induced proliferation of Nb2 cells involves tyrosine phosphorylation of the prolactin receptor and its associated tyrosine kinase JAK2.

The interaction of prolactin with its receptor in the Nb2 cell line has been shown to induce the phosphorylation of cell-associated proteins and mitogenesis. It has been reported previously that one of these proteins, phosphorylated upon prolactin stimulation, was a tyrosine kinase. We have identified this kinase as JAK2, and demonstrate its association with the prolactin receptor. In addition, we show that the prolactin receptor itself becomes tyrosine phosphorylated upon ligand stimulation in Nb2 cells. These actions are time-dependent and occur rapidly after prolactin stimulation, with first the kinase being activated within 5 min and then the receptor being phosphorylated maximally at 20 min. Moreover, phosphorylation of both JAK2 and the receptor as well as Nb2 cell proliferation are dependent on the concentration of lactogenic hormone, resulting in a bell-shaped response curve similar to that observed in the two site model of hGH action. This indicates that early events in signal transduction as well as later events like mitogenesis and proliferation involve prolactin receptor dimerization. Together these data indicate that the prolactin receptor in Nb2 cells is associated to JAK2 and that upon ligand stimulation, and receptor dimerization, the kinase and the receptor are tyrosine-phosphorylated, which represents the first event in the process of prolactin receptor signal transduction in Nb2 cells.

Blotting, Western↗
PubMed1993

The ezrin-like family of tyrosine kinase substrates: receptor-specific pattern of tyrosine phosphorylation and relationship to malignant transformation.

A method for the isolation of tyrosine kinases substrates was developed. The method takes advantage of immuno-affinity purification of an entire set of proteins phosphorylated by tyrosine kinases, followed by generation of antisera against the purified protein pool and immunological screening of bacterial expression libraries with these antisera. By applying this methodology to the study of the phosphorylation events triggered by activation of the epidermal growth factor receptors, we have isolated several cDNAs encoding novel putative tyrosine kinase substrates. One of these cDNAs encodes radixin, a protein belonging to the band 4.1 family of proteins and highly related to ezrin and moesin. We demonstrated that, despite a high degree of relatedness, these three proteins exhibit a distinct receptor-specific pattern of phosphorylation, raising the possibility that they might mediate receptor-specific cellular changes. In addition the generation of antibodies specific for either radixin, ezrin or moesin allowed us to show that a previously described tumor transplantation antigen is indeed ezrin, thus implicating this protein in the determination of the biological phenotype of certain tumors.

Amino Acid Sequence↗
PubMed1995

Inhibition of basic fibroblast growth factor-mediated tyrosine phosphorylation and protein synthesis by PD 145709, a member of the 2-thioindole class of tyrosine kinase inhibitors.

PD 145709, which represents one member of a new structural class of tyrosine kinase inhibitors, the thioindoles, inhibited basic fibroblast growth factor (bFGF)-mediated tyrosine phosphorylation in Swiss 3T3 murine fibroblasts. Half-maximal suppression was attained when cells were exposed for 2 h to 4.5 microM. Little or no inhibition of epidermal growth factor (EGF)- or platelet-derived growth factor (PDGF)-mediated tyrosine phosphorylation was observed at concentrations as high as 50 microM. The inhibition of bFGF-mediated phosphorylation occurred rapidly with maximal effects occurring after the cells were exposed to PD 145709 for 90 min. Once established, the inhibition was irreversible and remained for at least 2 h after PD 145709 was removed from the extracellular medium. PD 145709 also inhibited bFGF-mediated phosphorylation as well as FGF receptor autophosphorylation in a human breast carcinoma, MDA-MB-134, which overexpresses the FGF1 receptor. PD 145709 caused an increase of c-jun mRNA in response to EGF, PDGF, bFGF and serum. This effect may be due to the fact that this compound was a potent inhibitor of protein synthesis in cells and may cause superinduction of growth factor-mediated gene expression similar to other inhibitors of protein synthesis. Inhibition of protein synthesis occurred in fibroblasts exposed to PD 145709 with half-maximal inhibition at 0.5 microM, but not in an in vitro translation system at concentrations as high as 20 microM. This indicates that an intact viable cell is necessary for inhibition to occur and is compatible with a mechanism by which PD 145709 interferes with signals or protein factors that are involved with the initiation or protein synthesis.

3T3 Cells↗
PubMed1997

[Effect of tyrosine kinase and tyrosine phosphatase inhibitors on ATP- and thapsigargin-induced CA2+ entry in rat peritoneal macrophages].

The effect of two structurally distinct tyrosine kinase inhibitors, genistein (100 microM) and methyl-2, 5-dihydroxycinnamate (25 microM) on ATP- and thapsigargin-induced Ca2+ signals in Fura-2-loaded rat peritoneal macrophages was investigated. Both compounds were shown to inhibit ATP-evoked Ca2+ entry but not to release from internal stores. Both compounds also inhibit the store-dependent or "capacitative" Ca2+ influx stimulated by emptying the intracellular Ca2+ stores with endoplasmic Ca(2+)-ATPase inhibitor thapsigargin (100 nM). Genistein and methyl-2, 5-dihydroxycinnamate have no effect on Ca2+ release from intracellular stores. Tyrosine phosphatase inhibitor orthovanadate Na (50 microM) increases ATP-induced Ca2+ entry but does not prevent the inhibitory effect of genistein. These data are compatible with the role played by tyrosine phosphorylation in the control of Ca2+ entry in rat peritoneal macrophages.

Adenosine Triphosphate↗
PubMed1995

Nerve growth factor stimulates tyrosine phosphorylation and activation of Src homology-containing protein-tyrosine phosphatase 1 in PC12 cells.

Rat PC12 cells respond to extracellular peptide growth factors in at least two distinct ways. When treated with nerve growth factor (NGF) PC12 cells exit the cell cycle and differentiate to a neuronal phenotype, whereas when treated with epidermal growth factor, they proliferate. We examined the potential role of Src homology 2 (SH2)-containing protein tyrosine phosphatases (PTPs) in the differentiation process. PC12 cells express substantial amounts of both SH-PTP1 and 2. SH-PTP1, but not SH-PTP2, becomes tyrosine phosphorylated following NGF, but not epidermal growth factor treatment. The enzymatic activity of SH-PTP1 toward an exogenous substrate following NGF treatment is increased 2-fold. We found that SH-PTP1 binds to the NGF receptor TrkA in vitro and that anti-TrkA immunoprecipitates have PTP activity. These results show that SH-PTP1 is differentially phosphorylated and activated by NGF in PC12 cells and suggest that this activation may play a role in NGF-induced differentiation.

Animals↗
PubMed2000

Phosphorylation of tubulin tyrosine ligase: a potential mechanism for regulation of alpha-tubulin tyrosination.

The tubulin tyrosination/detyrosination cycle is a well-established posttranslational modification, which is carried out by two enzymes: Tubulin Tyrosine Ligase (TTL) and Tubulin Tyrosine Carboxypeptidase (TTCP). In this paper, I present evidence suggesting that the cycle itself is under the hierarchical control of reversible phosphorylation and that PKC mediated phosphorylation of TTL inhibits its activity, thereby preventing tubulin tyrosination. Phosphorylation of TTL is predicted to occur in a postulated Mg(++)/-ATP binding fold, leading to inhibition of Mg(++)/ATP binding and TTL mediated catalysis. The implications of such control are also discussed.

Amino Acid Sequence↗