scholarly journals Haemin enhancement of glucose transport in human lymphocytes: stimulation of protein tyrosine phosphatase and activation of p56lck tyrosine kinase

1993 ◽  
Vol 291 (1) ◽  
pp. 281-287 ◽  
Author(s):  
H M Lander ◽  
D M Levine ◽  
A Novogrodsky
Keyword(s):  
Tyrosine Kinase ◽  
Glucose Uptake ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Human Lymphocytes ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine ◽  
Ptpase Activity ◽  
Stimulation Of

Following our previous observation that haemin is mitogenic for human lymphocytes, we investigated the ability of haemin to enhance glucose uptake in these cells. We found that preincubation of human peripheral-blood mononuclear cells (PBMC) with haemin for 60 min increased up to 5-fold the rate of 2-deoxy-D-[1-3H]glucose uptake by the cells. Actinomycin D and cycloheximide did not inhibit the effect, and cytochalasin B completely blocked it. Among the metalloporphyrins tested (Fe-, Ni-, Co-, Zn- and Sn-protoporphyrin), only haemin (Fe-protoporphyrin) induced a marked increase in glucose uptake. Thiourea, a scavenger of oxygen free radicals, and 3-amino-1,2,4-triazole inhibited haemin-induced glucose uptake. Oxidants such as H2O2 and phenylarsine oxide were previously reported to stimulate protein tyrosine phosphorylation and to enhance glucose uptake. We found that incubation of PBMC with haemin resulted in an increase in protein tyrosine phosphatase (PTPase) activity, probably that identified as CD45. Similarly to haemin, we found that phytohaemagglutinin also enhanced PTPase activity. Haemin also activated the tyrosine kinase p56lck, which is negatively controlled by phosphorylation of Tyr-505 at the C-terminus, and increased protein tyrosine phosphorylation in these cells. Tyrphostins, specific inhibitors of tyrosine kinases, at low concentrations markedly enhanced glucose uptake and synergized with haemin in enhancing glucose uptake. At high doses, tyrphostins inhibited the effect of haemin. Taken together, we postulate that haemin enhancement of glucose uptake in human lymphocytes results from its stimulation of PTPase, followed by activation of tyrosine kinase p56lck, leading to an increase in protein tyrosine phosphorylation.

Anaplastic Lymphoma Kinase Is Activated through the Pleiotrophin/Receptor Protein Tyrosine Phosphatase (RPTP)β/ζ Signaling Pathway: A Unique Mechanism of Activation of Receptor Protein Tyrosine Kinases.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4355-4355
Author(s):  
Pablo Perez-Pinera ◽  
Wei Zhang ◽  
Zhaoyi Wang ◽  
James R. Berenson ◽  
Thomas F. Deuel
Keyword(s):  
Tyrosine Kinase ◽  
Signaling Pathway ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Kinases ◽  
Tyrosine Phosphatase ◽  
Receptor Protein ◽  
Protein Tyrosine ◽  
Anaplastic Lymphoma ◽  
Unique Mechanism

Abstract Anaplastic Lymphoma Kinase (ALK) is a receptor-type transmembrane tyrosine kinase (RTK) of the insulin receptor superfamily that structurally is most closely related to leukocyte tyrosine kinase. It was first discovered as a chimeric protein (NPM-ALK) of nucleophosmin and the C-terminal (kinase) domain of ALK in anaplastic large cell lymphomas (ALCL). NPM-ALK is constitutively active and generates the oncogenic signals that are the pathogenic mechanisms of these highly malignant cancers. The full-length ALK also is believed to have an important role in the pathogenesis of other human malignancies, since its expression is found in rhabdomyosarcomas, neuroblastomas, neuroectodermal tumors, glioblastomas, breast carcinomas, and melanomas. Recently it was proposed that pleiotrophin (PTN the protein, Ptn the gene) is the ligand that stimulates ALK to transduce signals to activate downstream targets. However, this proposal contrasted with earlier studies that demonstrated Receptor Protein Tyrosine Phosphatase (RPTP)β/ζ is the functional receptor for PTN. PTN was shown to inactivate RPTPβ/ζ and thereby permit the activity of different tyrosine kinases to increase tyrosine phosphorylation of the substrates of RPTPβ/ζ at the sites that are dephosphorylated by RPTPβ/ζ in cells not stimulated by PTN. Subsequent studies identified β-catenin, β-adducin, Fyn, GIT1/Cat-1, P190RhoGAP, and histone deacetylase 2 (HDAC-2) as downstream targets of the PTN/RPTPβ/ζ signaling pathway and demonstrated that their levels of tyrosine phosphorylation increase in PTN-stimulated cells. This diversity of PTN-regulated targets is one basis for the pleiotrophic activities of PTN. We now demonstrate that tyrosine phosphorylation of ALK is increased in PTN-stimulated cells through the PTN/RPTPβ/ζ signaling pathway. It is furthermore shown that ALK is activated in PTN-stimulated cells when it is expressed in cells without its extracellular domain, that β-catenin is a substrate of ALK, that the tyrosine phosphorylation site in β-catenin phosphorylated by ALK is the same site dephosphorylated by RPTPβ/ζ, and that PTN-stimulated tyrosine phosphorylation of β-catenin requires expression of ALK. The data suggest a unique mechanism to activate ALK; the data support a mechanism in which β-catenin is phosphorylated in tyrosine through the coordinated inactivation of RPTPβ/ζ, the activation of the tyrosine kinase activity of ALK, and the phosphorylation of β-catenin by ALK at the same site regulated by RPTPβ/ζ in PTN-stimulated cells. Since PTN often is inappropriately expressed in the same malignancies that express ALK, the data suggest a mechanism through which ALK signaling may contribute to those malignancies that express full length ALK through the activity of PTN to signal constitutively the same pathways as NPM-ALK in ALCL.

scholarly journals Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13.

1992 ◽  
Vol 12 (2) ◽  
pp. 836-846 ◽  
Author(s):  
T L Yi ◽  
J L Cleveland ◽  
J N Ihle
Keyword(s):  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Phosphatase ◽  
Human Gene ◽  
Tyrosine Phosphatase ◽  
Hematopoietic Cells ◽  
Protein Tyrosine Phosphatases ◽  
Hematopoietic Cell ◽  
Protein Tyrosine Phosphorylation ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine

Protein tyrosine phosphorylation has been implicated in the growth and functional responses of hematopoietic cells. Recently, approaches have been developed to characterize the protein tyrosine phosphatases that may contribute to regulation of protein tyrosine phosphorylation. One novel protein tyrosine phosphatase was expressed predominantly in hematopoietic cells. Hematopoietic cell phosphatase encodes a 68-kDa protein that contains a single phosphatase conserved domain. Unlike other known protein tyrosine phosphatases, hematopoietic cell phosphatase contains two src homology 2 domains. We also cloned the human homolog, which has 95% amino acid sequence identity. Both the murine and human gene products have tyrosine-specific phosphatase activity, and both are expressed predominantly in hematopoietic cells. Importantly, the human gene maps to chromosome 12 region p12-p13. This region is associated with rearrangements in approximately 10% of cases of acute lymphocytic leukemia in children.

Role of protein tyrosine phosphorylation in H2O2-induced activation of endothelial cell phospholipase D

1996 ◽  
Vol 271 (3) ◽  
pp. L400-L408 ◽  
Author(s):  
V. Natarajan ◽  
S. Vepa ◽  
R. S. Verma ◽  
W. M. Scribner
Keyword(s):  
Endothelial Cells ◽  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Tyrosine Kinase Inhibitors ◽  
Phospholipase D ◽  
Kinase Inhibitors ◽  
Tyrosine Phosphatase ◽  
Dependent Manner ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine

Oxidant-induced activation of phospholipase D (PLD) in bovine pulmonary artery endothelial cells (BPAEC) is independent of protein kinase C and calcium. In the present study, the effects of tyrosine kinase and protein tyrosine phosphatase (PTPase) inhibitors on hydrogen peroxide (H2O2)-induced PLD activation and protein tyrosine phosphorylation were examined in BPAEC. Pretreatment of BPAEC with putative tyrosine kinase inhibitors genistein, tyrphostin, and herbimycin attenuated H2O2 (1 mM)-induced PLD activation. The inhibitory effect of the tyrosine kinase inhibitors was highly specific for H2O2-induced modulation and showed no effect on PLD activation mediated by 12-O-tetradecanoylphorbol 13-acetate or bradykinin. Furthermore, addition of H2O2 increased in a time-dependent manner tyrosine phosphorylation of several proteins (17-200 kDa), as determined by immunoblot analysis with antiphosphotyrosine antibodies. H2O2-mediated protein tyrosine phosphorylation preceded PLD activation, and a good correlation was observed on the effect of genistein in H2O2-induced PLD activation and protein tyrosine phosphorylation. Addition of vanadate, a phosphotyrosine phosphatase inhibitor, synergistically increased both PLD activation and protein tyrosine phosphorylation mediated by H2O2. Moreover, vanadate by itself had minimal effect on basal PLD activity in BPAEC; however, at 10 microM vanadate, an increase in protein tyrosine phosphorylation was observed. In addition to vanadate, phenylarsine oxide and diamide potentiated H2O2-induced PLD activation. These results suggest that tyrosine kinase activation may be involved in H2O2-induced PLD activation in vascular endothelial cells.

scholarly journals Protein tyrosine phosphatase SAP-1 protects against colitis through regulation of CEACAM20 in the intestinal epithelium

2015 ◽  
Vol 112 (31) ◽  
pp. E4264-E4271 ◽  
Author(s):  
Yoji Murata ◽  
Takenori Kotani ◽  
Yana Supriatna ◽  
Yasuaki Kitamura ◽  
Shinya Imada ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Intestinal Epithelium ◽  
Protein Tyrosine Phosphatase ◽  
Molecular Mechanisms ◽  
Transmembrane Protein ◽  
Tyrosine Phosphatase ◽  
Intestinal Immunity ◽  
Protein Tyrosine

Intestinal epithelial cells contribute to regulation of intestinal immunity in mammals, but the detailed molecular mechanisms of such regulation have remained largely unknown. Stomach-cancer–associated protein tyrosine phosphatase 1 (SAP-1, also known as PTPRH) is a receptor-type protein tyrosine phosphatase that is localized specifically at microvilli of the brush border in gastrointestinal epithelial cells. Here we show that SAP-1 ablation in interleukin (IL)-10–deficient mice, a model of inflammatory bowel disease, resulted in a marked increase in the severity of colitis in association with up-regulation of mRNAs for various cytokines and chemokines in the colon. Tyrosine phosphorylation of carcinoembryonic antigen-related cell adhesion molecule (CEACAM) 20, an intestinal microvillus-specific transmembrane protein of the Ig superfamily, was greatly increased in the intestinal epithelium of the SAP-1–deficient animals, suggesting that this protein is a substrate for SAP-1. Tyrosine phosphorylation of CEACAM20 by the protein tyrosine kinase c-Src and the consequent association of CEACAM20 with spleen tyrosine kinase (Syk) promoted the production of IL-8 in cultured cells through the activation of nuclear factor-κB (NF-κB). In addition, SAP-1 and CEACAM20 were found to form a complex through interaction of their ectodomains. SAP-1 and CEACAM20 thus constitute a regulatory system through which the intestinal epithelium contributes to intestinal immunity.

scholarly journals CD148, a membrane protein tyrosine phosphatase, is able to induce tyrosine phosphorylation on human lymphocytes

1997 ◽  
Vol 57 (1-3) ◽  
pp. 101-103 ◽  
Author(s):  
E Palou ◽  
M.A de la Fuente-Garcı́a ◽  
J.M Nicolás ◽  
C Vilardell ◽  
J Vives ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Human Lymphocytes ◽  
Protein Tyrosine

Protein tyrosine phosphorylation, cellular Ca2+, and Ca2+ sensitivity for contraction of smooth muscle

1994 ◽  
Vol 72 (11) ◽  
pp. 1434-1439 ◽  
Author(s):  
Joseph Di Salvo ◽  
Gabrielle Pfitzer ◽  
Lori A. Semenchuk
Keyword(s):  
Smooth Muscle ◽  
Tyrosine Phosphorylation ◽  
Vascular Smooth Muscle Cells ◽  
Adrenergic Receptors ◽  
Kinase Activity ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphorylation ◽  
Tyrosine Kinase Activity ◽  
Protein Tyrosine ◽  
Stimulation Of

Our studies are guided by the novel hypothesis that protein tyrosine phosphorylation is an important mechanism for regulating contraction of smooth muscle. Several lines of evidence are reviewed which suggest that enhanced tyrosine phosphorylation participates in mechanisms that regulate cytosolic Ca2+ and Ca2+ sensitivity for contraction. First, vanadate-induced contraction of guinea-pig taenia coli is functionally linked to enhanced protein tyrosine phosphorylation of at least three substrates, apparently resulting from vanadate-mediated inhibition of protein tyrosine phosphatase activity. Second, vanadate-induced contraction is dependent on extracellular Ca2+. Third, increases in cytosolic Ca2+ resulting from stimulation of αi-adrenergic receptors in cultured canine vascular smooth muscle cells are associated with enhanced tyrosine phosphorylation and are inhibited by genistein, a potent inhibitor of tyrosine kinase activity. Fourth, genistein markedly and reversibly suppresses Ca2+ sensitivity for contraction in ileal longitudinal smooth muscle permeabilized with staphylococcal α-toxin. Moreover, the same or similar substrates (e.g., 42–45, 70, 80–85, 95, 100, 110, 116, and 205 kDa) are tyrosine phosphorylated in response to Ca2+ or stimulation of muscarinic or αi-adrenergic receptors. Collectively, these data strongly suggest that tyrosine phosphorylation is an important mechanism for regulation of smooth muscle contraction.Key words: actin–myosin interaction, calcium sensitivity, genistein, permeabilized smooth muscle, tyrosine kinase activity, tyrosine phosphatase activity, vascular smooth muscle cells, vanadate.

scholarly journals Protein Tyrosine Phosphatase 1B Attenuates Growth Hormone-Mediated JAK2-STAT Signaling

2003 ◽  
Vol 23 (11) ◽  
pp. 3753-3762 ◽  
Author(s):  
Feng Gu ◽  
Nadia Dubé ◽  
Jin Wook Kim ◽  
Alan Cheng ◽  
Maria de Jesus Ibarra-Sanchez ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Tyrosine Kinase ◽  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Cytokine Signaling ◽  
Tyrosine Kinase Domain ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Ptp 1B

ABSTRACT Protein tyrosine phosphatase-1B (PTP-1B) attenuates insulin, PDGF, EGF, and IGF-I signaling by dephosphorylating tyrosine residues located in the tyrosine kinase domain of the corresponding receptors. More recently, PTP-1B was shown to modulate the action of cytokine signaling via the nonreceptor tyrosine kinase JAK2. Transmission of the growth hormone (GH) signal also depends on JAK2, raising the possibility that PTP-1B modulates GH action. Consistent with this hypothesis, GH increased the abundance of tyrosine-phosphorylated JAK2 associated with a catalytically inactive mutant of PTP-1B. GH-induced JAK2 phosphorylation was greater in knockout (KO) than in wild-type (WT) PTP-1B embryonic fibroblasts and resulted in increased tyrosine phosphorylation of STAT3 and STAT5, while overexpression of PTP-1B reduced the GH-mediated activation of the acid-labile subunit gene. To evaluate the in vivo relevance of these observations, mice were injected with GH under fed and fasted conditions. As expected, tyrosine phosphorylation of JAK2 and STAT5 occurred readily in the livers of fed WT mice and was almost completely abolished during fasting. In contrast, resistance to the action of GH was severely impaired in the livers of fasted KO mice. These results indicate that PTP-1B regulates GH signaling by reducing the extent of JAK2 phosphorylation and suggest that PTP-1B is essential for limiting the action of GH during metabolic stress such as fasting.

scholarly journals Hyaluronan and the hyaluronan receptor RHAMM promote focal adhesion turnover and transient tyrosine kinase activity.

1994 ◽  
Vol 126 (2) ◽  
pp. 575-588 ◽  
Author(s):  
C L Hall ◽  
C Wang ◽  
L A Lange ◽  
E A Turley
Keyword(s):  
Tyrosine Kinase ◽  
Cell Motility ◽  
Tyrosine Phosphorylation ◽  
Focal Adhesion ◽  
Peptide Sequence ◽  
Protein Tyrosine Phosphorylation ◽  
Protein Tyrosine ◽  
Cell Locomotion ◽  
Focal Adhesion Turnover ◽  
Stimulation Of

The molecular mechanisms whereby hyaluronan (HA) stimulates cell motility was investigated in a C-H-ras transformed 10T 1/2 fibroblast cell line (C3). A significant (p < 0.001) stimulation of C3 cell motility with HA (10 ng/ml) was accompanied by an increase in protein tyrosine phosphorylation as detected by anti-phosphotyrosine antibodies using immunoblot analysis and immunofluorescence staining of cells. Tyrosine phosphorylation of several proteins was found to be both rapid and transient with phosphorylation occurring within 1 min of HA addition and dissipating below control levels 10-15 min later. These responses were also elicited by an antibody generated against a peptide sequence within the HA receptor RHAMM. Treatment of cells with tyrosine kinase inhibitors (genistein, 10 micrograms/ml or herbimycin A, 0.5 micrograms/ml) or microinjection of anti-phosphotyrosine antibodies inhibited the transient protein tyrosine phosphorylation in response to HA as well as prevented HA stimulation of cell motility. To determine a link between HA-stimulated tyrosine phosphorylation and the resulting cell locomotion, cytoskeletal reorganization was examined in C3 cells plated on fibronectin and treated with HA or anti-RHAMM antibody. These agents caused a rapid assembly and disassembly of focal adhesions as revealed by immunofluorescent localization of vinculin. The time course with which HA and antibody induced focal adhesion turnover exactly paralleled the induction of transient protein tyrosine phosphorylation. In addition, phosphotyrosine staining colocalized with vinculin within structures in the lamellapodia of these cells. Notably, the focal adhesion kinase, pp125FAK, was rapidly phosphorylated and dephosphorylated after HA stimulation. These results suggest that HA stimulates locomotion via a rapid and transient protein tyrosine kinase signaling event mediated by RHAMM. They also provide a possible molecular basis for focal adhesion turnover, a process that is critical for cell locomotion.

Protein tyrosine phosphatase containing SH2 domains: characterization, preferential expression in hematopoietic cells, and localization to human chromosome 12p12-p13

1992 ◽  
Vol 12 (2) ◽  
pp. 836-846
Author(s):  
T L Yi ◽  
J L Cleveland ◽  
J N Ihle
Keyword(s):  
Tyrosine Phosphorylation ◽  
Protein Tyrosine Phosphatase ◽  
Human Gene ◽  
Tyrosine Phosphatase ◽  
Hematopoietic Cells ◽  
Protein Tyrosine Phosphatases ◽  
Hematopoietic Cell ◽  
Protein Tyrosine Phosphorylation ◽  
Tyrosine Phosphatases ◽  
Protein Tyrosine

Protein tyrosine phosphorylation has been implicated in the growth and functional responses of hematopoietic cells. Recently, approaches have been developed to characterize the protein tyrosine phosphatases that may contribute to regulation of protein tyrosine phosphorylation. One novel protein tyrosine phosphatase was expressed predominantly in hematopoietic cells. Hematopoietic cell phosphatase encodes a 68-kDa protein that contains a single phosphatase conserved domain. Unlike other known protein tyrosine phosphatases, hematopoietic cell phosphatase contains two src homology 2 domains. We also cloned the human homolog, which has 95% amino acid sequence identity. Both the murine and human gene products have tyrosine-specific phosphatase activity, and both are expressed predominantly in hematopoietic cells. Importantly, the human gene maps to chromosome 12 region p12-p13. This region is associated with rearrangements in approximately 10% of cases of acute lymphocytic leukemia in children.

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