Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

More than two isoforms have been identified for angiotensin receptors based on their ligand selectivity. The objective of this study is to determine the molecular structure of angiotensin type 2 receptor (AT2), whose physiological functions are still an enigma despite extensive studies on its distribution in fetal tissues. We expression-cloned a cDNA of an affinity-purified AT2 from rat pheochromocytoma cells (PC12w). The AT2 cDNA clone comprises 2,868 nucleotides and encodes a 363 amino acid protein with seven putative transmembrane domains. The dissociation constant for its binding to 125I-CGP42112A, an AT2-specific ligand, was 0.11 +/- 0.01 nM. Its binding to 0.5 nM 125I-[Sar1,Ile8]-Ang II was not inhibited by Dup 753 but by PD123319 (IC50 = 1.7 +/- 0.2 nM). These binding features are characteristic of angiotensin type 2 receptor. The amino acid sequence analysis of the purified AT2 corroborated the amino terminus of the deduced primary structure of AT2. Angiotensin type 1 receptor (AT1) is the most closely related to AT2 but with only 32% amino acid sequence identity. Angiotensin II attenuated membrane-associated protein tyrosine phosphatase activity in the COS-7 cells stably expressing AT2 through a pertussis toxin-sensitive G protein. However, the physiological function of AT2 in the fetal kidney is still unresolved.
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PMID:Molecular structure and function of angiotensin type 2 receptor. 769 90

SH-PTP1 is a protein tyrosine phosphatase (PTP) predominantly expressed in haematopoietic cells and containing two src homology-2 (SH2) domains. Here we report that SH-PTP1 is phosphorylated on both serine and tyrosine residues in response to thrombin or phorbol myristate acetate (PMA), which increased by 60 and 40%, respectively, SH-PTP1 activity. Thrombin-induced phosphorylation of SH-PTP1 is an early signalling event (maximal within 10 s) involving neither integrin signalling, nor calcium, nor release of ADP or thromboxane A2. Moreover, in contrast with PMA, the effect of thrombin on the tyrosine phosphorylation of SH-PTP1 was hardly affected by GF109203X, a specific protein kinase C (PKC) inhibitor. Finally, phosphorylation of SH-PTP1 could be provoked in permeabilized platelets by thrombin or GTP gamma S. This was abolished by pertussis toxin, the specificity of this effect being verified with the megakaryocytic cell line Dami cell. Our data thus identify SH-PTP1 as an in vivo substrate of a putative protein tyrosine kinase linked to the thrombin receptor by a Gi protein. This might offer some clue to unravel the mechanism of thrombin not only in platelets but also in nucleated cells, where its mitogenic effect is known to involve pertussis toxin-sensitive G-proteins, tyrosine phosphorylation and the ras pathway.
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PMID:Tyrosine phosphorylation of an SH2-containing protein tyrosine phosphatase is coupled to platelet thrombin receptor via a pertussis toxin-sensitive heterotrimeric G-protein. 778 4

Effects of insulin and IGF-1 (insulin-like growth factor-1) on K+ channel opener-induced/glibenclamide-sensitive K+ currents were studied using follicle-enclosed Xenopus oocytes. Both insulin (4 x 10(-9)-4 x 10(-6) M) and IGF-1 (4 x 10(-10)-4 x 10(-7) M) increased the cromakalim-induced K+ currents in a concentration-dependent manner. The current-facilitating effect of IGF-1 was about ten times as potent as that of insulin. Treatment of the oocyte with pertussis toxin (2 micrograms/ml) suppressed the current-potentiating effects of insulin and IGF-1 by about 60%. Although phenylarsine oxide (1-100 microM), a putative inhibitor of protein tyrosine phosphatase, also facilitated the K+ currents, the current enhancing effects were not affected by pertussis toxin. These results suggest that insulin and IGF-1 potentiate the glibenclamide-sensitive K+ current by activating IGF-1 receptor and that pertussis toxin-sensitive G-protein may be associated with these effects.
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PMID:Potentiation by insulin and insulin-like growth factor-1 of glibenclamide-sensitive K+ currents in follicle-enclosed Xenopus oocytes. 780 61

There are two major isoforms of the angiotensin II receptor, type 1 (AT1) and type 2 (AT2). AT2 is distinguished from AT1 with respect to its ligand selectivity, its insensitivity to non-hydrolyzable GTP analogues, and its as yet unidentified biological functions. In the present study we have expression-cloned AT2 cDNA from a cDNA library of a rat pheochromocytoma cell line (PC12w). Rat AT2 cDNA encodes a 363-amino acid protein that has seven transmembrane domains. AT1 is the closest in homology to AT2 but with only a 32% identity of amino acid sequence. Stably expressed in COS-7 cells, the receptor showed selective binding to AT2-specific ligands PD123319 and CGP42112A but not to the AT1-specific ligand, losartan. Northern blot analysis revealed that the mRNA of rat AT2 was expressed not only in PC12w cells but also in the adrenal glands and in the inferior olive of the brain, both of which are known to contain AT2 type binding sites. The expressed AT2 receptor mediated angiotensin II-induced inhibition of protein tyrosine phosphatase, an action that was dependent on a pertussis toxin-sensitive G-protein-coupled mechanism in COS-7 cells. The AT2-specific ligand CGP42112A was an agonist rather than antagonist in the inhibition of phosphotyrosine phosphatase. AT2 did not cause a decrease in cGMP in PC12w or COS-7 cells expressing AT2 stably. These results indicate that the AT2 receptor is structurally and functionally different from AT1 and suggest novel functional roles of the renin-angiotensin system in cross-talk with phosphotyrosine signaling by modulating protein phosphotyrosine levels.
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PMID:Molecular cloning of a novel angiotensin II receptor isoform involved in phosphotyrosine phosphatase inhibition. 822 11

Somatostatin receptors (sstr) subtypes 1-5 were transiently expressed in NIH 3T3 cells stably transformed with Ha-Ras(G12V) to assess the ability of each receptor to stimulate protein tyrosine phosphatase (PTPase) activity in vitro. Treatment of membranes from sstr2-, sstr3-, or sstr4-expressing cells with somatostatin-14 plus guanyl-5'-yl imidodiphosphate (GMPPNP) increased PTPase activity, and this stimulation was pertussis toxin-sensitive. Somatostatin alone, GMPPNP alone, or somatostatin plus GDP were ineffective under these conditions. sstr1 and sstr5 failed to increase PTPase activity although both receptors were expressed, as assessed by appearance of high-affinity binding sites for [125I-Tyr11]somatostatin-14. Somatostatin plus GMPPNP stimulated PTPase activity in vitro when sstr2 was coexpressed with wild type PTP1B or a Cys to Ser (C/S), catalytically inactive PTP1B or with wild type SH2-domain containing PTPase SHP-2. However, coexpression with catalytically inactive C/S SHP-2 abrogated this response. Thus, three of the five cloned sstr's can couple to activate PTPase in this cellular background. Abrogation of the response by C/S SHP-2 strongly suggests, but does not prove, a role for SHP-2 in the mechanism.
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PMID:Activation in vitro of somatostatin receptor subtypes 2, 3, or 4 stimulates protein tyrosine phosphatase activity in membranes from transfected Ras-transformed NIH 3T3 cells: coexpression with catalytically inactive SHP-2 blocks responsiveness. 921 54

Angiotensin II type 2 (AT2) receptors are involved in the inhibition of cell proliferation as well as in apoptosis and neuronal differentiation, through intracellular signalling pathways that remain poorly defined. The present study examines the effect of AT2-receptor stimulation on growth-factor-induced pathways leading to the activation of mitogen-activated protein (MAP) kinases. In N1E-115 neuroblastoma cells, AT2 receptors inhibit the activity of MAP kinases induced by serum as well as by epidermal growth factor. The inhibitory effect of angiotensin II (Ang II) is rapid and transient, and affects both ERK1 and ERK2 (extracellular signal-related protein kinase) isoforms of the enzyme. AT2-mediated MAP kinase inactivation is not sensitive to pertussis toxin or okadaic acid, but involves a vanadate-sensitive protein tyrosine phosphatase (PTP). Expression of MAP kinase phosphatase-1 (MKP-1) is not significantly modified upon AT2-receptor activation, and insensitivity to actinomycin D also rules out transcriptional induction of other MKPs as a possible mechanism for AT2-mediated inactivation of MAP kinases. In addition, we report here that both in N1E-115 cells and in Chinese hamster ovary cells expressing recombinant human AT2 receptors, Ang II rapidly stimulates the catalytic activity of SHP-1, a soluble PTP that has been implicated in termination of signalling by cytokine and growth-factor receptors. These findings thus demonstrate functional negative cross-talk between heptahelical AT2 receptors and receptor tyrosine kinases, and suggest that SHP-1 tyrosine phosphatase is an early transducer of the AT2 receptor signalling pathway.
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PMID:Angiotensin II type 2 receptors mediate inhibition of mitogen-activated protein kinase cascade and functional activation of SHP-1 tyrosine phosphatase. 923 Jan 27

Angiotensin II (ANG II) has long been known for its pressor and growth-promoting effects, which are both mediated by the AT1 receptor. By contrast, the AT2 receptor has recently been reported to mediate inhibition of proliferation through as yet undefined mechanisms. We report here that in bovine adrenal fasciculata cells ANG II by itself does not affect growth but inhibits basic fibroblast growth factor (bFGF)-induced DNA synthesis and blocks the cells in G1 phase. Consistent with this, ANG II inhibits cyclin D1 expression and cyclin D1-associated kinase activity. The antimitogenic effect of ANG II is partly mimicked by the AT2-selective agonist CGP-42112. It is also blocked partly and in an additive fashion by the AT1- and AT2-selective antagonists losartan and PD-123319, indicating the contribution of both receptor subtypes to this response. AT1-dependent antiproliferation is selectively blocked by the cyclooxygenase inhibitor indomethacin and restored by prostaglandin E2, whereas AT2-receptor-mediated inhibition of growth is suppressed by the tyrosine phosphatase inhibitors orthovanadate and bpV(pic). Both pathways are, however, pertussis toxin sensitive. We hypothesize that, in fasciculata cells, the AT1 receptor inhibits bFGF-induced proliferation by stimulating prostaglandin synthesis, whereas the AT2 receptor mediates its effect through a pathway that requires protein tyrosine phosphatase activation.
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PMID:ANG II AT1 and AT2 receptors both inhibit bFGF-induced proliferation of bovine adrenocortical cells. 935 77

Apoptosis associated oligonucleosomal fragmentation of DNA can result from the activation of endonucleases that exhibit different pH optima and are either sensitive or insensitive to divalent cations. DNA fragmentation due to activation of cation sensitive endonucleases occurs in the absence of a change in intracellular pH whereas intracellular acidification is a feature of apoptosis characterized by activation of cation insensitive acidic endonuclease. We have reported earlier that somatostatin (SST) induced DNA fragmentation and apoptosis is signaled in a receptor subtype selective manner uniquely via human somatostatin receptor subtype 3 (hSSTR3). In the present study we investigated the pH dependence and cation sensitivity of endonuclease induced in hSSTR3 expressing CHO-K1 cells by the SST agonist octreotide (OCT) and its effect on intracellular pH. We show that OCT induced apoptosis is associated with selective stimulation of a divalent cation insensitive acidic endonuclease. The intracellular pH of of cells undergoing OCT induced apoptosis was 0.9 pH units lower than that of control cells. The effect of OCT on endonuclease and pH was inhibited by orthovanadate as well as by pretreatment with pertussis toxin, suggesting that hSSTR3 initiated cytotoxic signaling is protein tyrosine phosphatase mediated and is G protein dependent. These findings suggest that intracellular acidification and activation of acidic endonuclease mediate wild type p53 associated apoptosis signaled by hormones acting via G protein coupled receptors.
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PMID:G protein coupled receptor signaled apoptosis is associated with activation of a cation insensitive acidic endonuclease and intracellular acidification. 943 24

SHPS-1 is an approximately 120 kDa glycosylated receptor like protein that contains three immunoglobulin-like domains in its extracellular region as well as four potential tyrosine phosphorylation and SRC homology 2 (SH2) domain binding sites in its cytoplasmic region. Lysophosphatidic acid (LPA) stimulated the rapid tyrosine phosphorylation of SHPS-1 and its subsequent association with SHP-2, a protein tyrosine phosphatase containing SH2 domains in Rat-1 fibroblasts. LAP-induced tyrosine phosphorylation of SHPS-1 was inhibited by Clostridium botulinum C3 exoenzyme (which inactivates RHO) but not by pertussis toxin. The protein kinase C activator phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) also stimulated tyrosine phosphorylation of SHPS-1; however, down-regulation of protein kinase C by prolonged exposure of cells to TPA did not affect LAP-induced tyrosine phosphorylation of SHPS-1. LPA-induced tyrosine phosphorylation of SHPS-1 was markedly reduced in either focal adhesion kinase (FAK)-deficient mouse cells or CHO cells overexpressing the tyrosine kinase CSK. Overexpression of a catalytically inactivate SHP-2 markedly inhibited MAP kinase activation in response to low concentrations of LPA in CHO cells, whereas overexpression of a wild-type SHPS-1 did enhance this effect of LPA. Furthermore, MAP kinase activation in response to a low concentration of LPA was inhibited by botulinum C3 exoenzyme. These results indicate that LPA-induced tyrosine phosphorylation of SHPS-1 and its association with SHP-2 may be mediated by a RHO-dependent pathway that includes FAK and a SRC family kinase. Thus, in addition to its role in receptor tyrosine kinase-mediated MAP kinase activation, the formation of a complex between SHPS-1 and SHP-2 may, in part, play an important role in the activation of MAP kinase in response to low concentrations of LPA.
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PMID:Lysophosphatidic acid-induced association of SHP-2 with SHPS-1: roles of RHO, FAK, and a SRC family kinase. 966 35

Degranulation of eosinophils and subsequent release of toxic granule proteins play a key role in allergic diseases such as bronchial asthma. We have previously shown that stimulation of eosinophils with immobilized secretory immunoglobulin A (sIgA) induced the phosphorylation of several proteins including 51-, 65-, 73-, 78-, 100-, 105- and 113-kD proteins. Pervanadate, a protein tyrosine phosphatase inhibitor, also induced at least 7 tyrosine phosphorylated proteins including those observed with immobilized sIgA. Pervanadate also induced inositol phosphate (IP) production and degranulation of eosinophils in a concentration-dependent manner. Eosinophil production of IP and degranulation as well as tyrosine phosphorylation of proteins induced by sIgA were completely inhibited by a tyrosine kinase inhibitor, genistein, and pertussis toxin (PTX), suggesting the involvement of both the PTX-sensitive guanine nucleotide-binding (G) protein and protein tyrosine kinases (PTK) in sIgA-induced activation of eosinophils. In contrast, PTX did not affect tyrosine phosphorylation induced by sIgA or pervanadate. Furthermore, pervanadate-induced IP production was partially inhibited by PTX. Finally, a phospholipase C-gamma2 isoform was tyrosine phosphorylated by pervanadate, but not by sIgA. These findings suggest that at least two different pathways, i.e. PTK-mediated G protein-dependent or -independent PLC activation, are involved in the activation of human eosinophils.
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PMID:Signal transduction in activation of human eosinophils: G protein-dependent and -independent pathways. 975 1


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