A role for guanine-nucleotide-binding proteins in mediating T-cell-receptor coupling to inositol phospholipid hydrolysis in a murine T-helper (type II) lymphocyte clone

Bonvini, Ezio; DeBell, Karen E.; Taplits, Michael; Brando, Clara; Laurenza, Antonio; Seamon, Kenneth B.; Hoffman, Thomas

doi:10.1042/bj2750689

Cited by 15 publications

(20 citation statements)

References 51 publications

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“…For example,. several growth factors and lymphocyte cell-surface antigens whose actions have been proposed to be mediated by members of the src subfamily (1)(2)(3)(4)(5)(6)(7)(8)(9) also modulate G-protein functioning (10,11) and adenylyl cyclase activity (12,13). In addition, two enzymes involved in inositol phospholipid metabolism, which is highly regulated by G proteins, may be targets of phosphorylation by activated src gene products (1,14).…”

mentioning

confidence: 99%

Tyrosine phosphorylation of G protein alpha subunits by pp60c-src.

Hausdorff

Pitcher

Luttrell

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

106

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A number of lines of evidence suggest that cross-talk exists between the cellular signal transduction pathways involving tyrosine phosphorylation catalyzed by members of the pp6OC-srC kinase family and those mediated by guanine nucleotide regulatory proteins (G proteins). In this study, we explore the possibility that direct interactions between pp60' and G proteins may occur with functional consequences. Preparations of pp6cc isolated by immunoprecipitation phosphorylate on tyrosine residues the purified G-protein a subunits (Ga) of several heterotrimeric G proteins. Phosphorylation is highly dependent on G-protein conformation, and Ga(GDP) uncomplexed by Pr subunits appears to be the preferred substrate. In functional studies, phosphorylation of stimulatory Ga (Ga.) modestly increases the rate of binding of guanosine 5'-[y-[35S]thiojtriphosphate to G. as well as the receptor-stimulated steady-state rate of GTP hydrolysis by Gs.Heterotrimeric G proteins may represent a previously unappreciated class of potential substrates for ppW.SrI.The oncogenes of many retroviruses encode tyrosine-specific protein kinases that are presumed to phosphorylate cellular proteins involved in the control of cell growth and differentiation. Many of these kinases belong to the src family of kinases by virtue of their structural homology with the oncogene product (pp60v-src) encoded by Rous sarcoma virus. Members of this family are cytoplasmic proteins that are myristoylated, associated with cellular membranes, and may mediate the actions of diverse cell-surface receptors (1-3).A number of lines of experimental evidence point to the existence of functional interactions between activated members of the pp6OC-src family and elements in the signal transduction pathways mediated by guanine nucleotide-binding regulatory proteins (G proteins). For example,. several growth factors and lymphocyte cell-surface antigens whose actions have been proposed to be mediated by members of the src subfamily (1-9) also modulate G-protein functioning (10,11) and adenylyl cyclase activity (12,13). In addition, two enzymes involved in inositol phospholipid metabolism, which is highly regulated by G proteins, may be targets of phosphorylation by activated src gene products (1,14). Furthermore, overexpression .of avian pp6OC-src in fibroblasts results in enhanced intracellular cAMP levels and adenylyl cyclase activity in response to B-adrenergic hormones, which act via the stimulatory G protein (GJ) (15,16).The molecular nature of these putative interactions has remained obscure. However, the observation that pp60c-src is a major contaminant in some highly purified G-protein preparations (17) suggests the possibility of a direct association between pp6Oc-src and G proteins. In this study, we examined the abilities of purified G proteins to serve as substrates for phosphorylation by pp60C-src. Immunoprecipitations were performed by using the rodent/avian pp60c-src-specific monoclonal antibody GD11 (27). Specifically, 20 1.l of a 1:10 dilution of GD11 ...

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mentioning

confidence: 99%

Tyrosine phosphorylation of G protein alpha subunits by pp60c-src.

Hausdorff

Pitcher

Luttrell

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

106

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“…Functional interactions between tyrosine phosphorylation and the signal transduction pathways mediated TYROSINE KINASE INHIBITION AND PINEAL cAMP 1601 by G proteins have been reported in several reports (Ball et al, 1990;Bonvini et al, 1991 ;Hausdorff et al, 1992) . In this study, we have investigated the interaction between tyrosine kinase or kinases and the G protein-coupled cAMP signaling pathway in rat pinealocytes.…”

Section: Discussionmentioning

confidence: 92%

“…Several lines of evidence suggest that cross talk exists between cellular signal transduction pathways that involve tyrosine phosphorylation and those mediated by G proteins . Different growth factors whose actions have been proposed to be mediated by tyrosine kinase also modulate G-protein coupling (Ball et al ., 1990 ;Bonvini et al ., 1991 ;Hausdorff et al ., 1992) . One such example is the involvement of tyrosine kinase in the growth factor receptor-coupled PLC signal transduction mechanism and that phosphoinositide phosphorylation is regulated in part by tyrosine phosphorylation (Meisenhelder et al, 1989 ;Gaudette and Holub, 1990 ;Goldschmidt-Clermont et al ., 1991) .…”

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confidence: 99%

Potentiation of Agonist‐Stimulated Cyclic AMP Accumulation by Tyrosine Kinase Inhibitors in Rat Pinealocytes

Ho¹,

Wiest²,

Ogiwara³

et al. 1995

Journal of Neurochemistry

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To study cross‐talk mechanisms in rat pinealocytes, the role of tyrosine kinase or kinases in the regulation of adrenergic‐stimulated cyclic AMP production was investigated. Both norepinephrine‐ and isoproterenol‐stimulated cyclic AMP accumulation were increased by two distinct tyrosine kinase inhibitors, genistein or erbstatin, in a concentration‐dependent manner. A similar increase was observed with two other inhibitors, tyrphostin B44 and herbimycin. In contrast, daidzein, an inactive analogue of genistein, was ineffective; whereas vanadate, a phosphotyrosine phosphatase inhibitor, reduced the adrenergic‐stimulated cyclic AMP accumulation. The tyrosine kinase inhibitors were effective in potentiating the cholera toxin‐or forskolin‐stimulated cyclic AMP accumulation, indicating that their sites of action are at the postreceptor level. Neither an activator nor inhibitors of protein kinase C influenced the potentiation of the cyclic AMP responses by genistein, suggesting that the potentiation effect by tyrosine kinase inhibitors does not involve the phospholipase C/protein kinase C pathway. However, when the phosphodiesterase was inhibited by isobutylmethylxanthine, genistein failed to potentiate and vanadate did not inhibit the adrenergic‐stimulated cyclic AMP accumulation, indicating that the phosphodiesterase is a probable site of action for these inhibitors. These results suggest that cyclic AMP metabolism in the pinealocytes is tonically inhibited by tyrosine kinase acting on the cyclic AMP phosphodiesterase.

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“…Unless otherwise indicated this included 0.5 mM ATP and free-Ca*+ was buffered at 150 nM; details of buffer composition are in [27]. Antibody was added to the cells and after 2 rnin cross-linked with sheep-anti-mouse IgG (5 Fg/ml) followed, a further 2 min later, by transfer to 37°C where the cells permeabilize upon warming [28]. The final volume in both intact and permeabilized cell incubations was 100 pl.…”

Section: Dag and Pa Determinationsmentioning

confidence: 99%

Selective coupling of the T cell antigen receptor to phosphoinositide‐derived diacylglycerol production in HPB‐ALL T cells correlates with CD45‐regulated p59^fyn activity

1993

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In HPB-ALL T-cells the p59fyn tyrosine kinase is regulated by the CD45 phosphotyrosine phosphatase and plays a critical role in coupling the T cell receptor (TCR) to the generation of intracellular signals which include diacylglycerol (DAG) production and protein kinase C activation. The aim of this study was to determine the phospholipid pools from which the DAG is generated and to identify which phospholipase activities are regulated by the TCR. When CD45+ cells were pre-labeled with [3H]arachidonic acid, CD3-antigen cross-linking stimulated negligible increases in both [3H]DAG and [3H]phosphatidic acid (PA). However, CD3 monoclonal antibody (mAb) induced an increase of 300% in [3H]PA when the cells were permeabilized with streptolysin-O, and this correlated with increased levels of protein tyrosine phosphorylation. Stimulation of [3H]PA production upon CD3 cross-linking was 77% lower in permeabilized CD45- cells than in CD45+ cells, consistent with the reduced activity of p59fyn in CD45- cells. The stimulated production of PA was not mediated by activation of phospholipase D (PLD), although the presence of a G-protein-regulated PLD activity was established. The CD3-induced increase in total inositol phosphates (InsP) in permeabilized cells was similar to the stimulated production of [3H]PA production in both CD45+ and CD45- cells. Dose-response curves for InsP and PA production triggered by CD3 mAb were super-imposable and the production of InsP and PA over a range of Ca2+ concentrations was comparable. Differential labeling of phospholipids with 3H-labeled fatty acids revealed that CD3-induced PA production reflected incorporation of label into the phosphatidylinositol pool. Our data suggest that in HPB-ALL cells the production of DAG following CD3-antigen cross-linking can be fully accounted for by the selective coupling of the TCR to breakdown of phosphatidylinositol-(4,5)-bisphosphate as the result of phospholipase C gamma 1 activation. This event correlates with the activity of the CD45-regulated TCR-associated tyrosine kinase, p59fyn.

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A role for guanine-nucleotide-binding proteins in mediating T-cell-receptor coupling to inositol phospholipid hydrolysis in a murine T-helper (type II) lymphocyte clone

Cited by 15 publications

References 51 publications

Tyrosine phosphorylation of G protein alpha subunits by pp60c-src.

Tyrosine phosphorylation of G protein alpha subunits by pp60c-src.

Potentiation of Agonist‐Stimulated Cyclic AMP Accumulation by Tyrosine Kinase Inhibitors in Rat Pinealocytes

Selective coupling of the T cell antigen receptor to phosphoinositide‐derived diacylglycerol production in HPB‐ALL T cells correlates with CD45‐regulated p59^fyn activity

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A role for guanine-nucleotide-binding proteins in mediating T-cell-receptor coupling to inositol phospholipid hydrolysis in a murine T-helper (type II) lymphocyte clone

Cited by 15 publications

References 51 publications

Tyrosine phosphorylation of G protein alpha subunits by pp60c-src.

Tyrosine phosphorylation of G protein alpha subunits by pp60c-src.

Potentiation of Agonist‐Stimulated Cyclic AMP Accumulation by Tyrosine Kinase Inhibitors in Rat Pinealocytes

Selective coupling of the T cell antigen receptor to phosphoinositide‐derived diacylglycerol production in HPB‐ALL T cells correlates with CD45‐regulated p59fyn activity

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Selective coupling of the T cell antigen receptor to phosphoinositide‐derived diacylglycerol production in HPB‐ALL T cells correlates with CD45‐regulated p59^fyn activity