Release of the glycosylphosphatidylinositol-anchored enzyme ecto-5′-nucleotidase by phospholipase C: catalytic activation and modulation by the lipid bilayer

Lehto, Marty T.; Sharom, Frances J.

doi:10.1042/bj3320101

Cited by 59 publications

(38 citation statements)

References 45 publications

(59 reference statements)

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“…The removal of the GPI lipid moiety in vitro was reported to cause significant alterations in enzymatic activities [200][201][202][203] and ligand binding properties [204][205][206], thus it is quite likely that some GPI-anchored proteins in the membrane are actually reservoirs of inactive proteins that can be activated and rapidly released by GPI cleavage.…”

Section: Release Of Gpi-anchored Proteins By Gpi Cleavagementioning

confidence: 99%

Shedding and uptake of gangliosides and glycosylphosphatidylinositol-anchored proteins

Lauc

Heffer-Lauc

2006

Biochimica et Biophysica Acta (BBA) - General Subjects

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Section: Release Of Gpi-anchored Proteins By Gpi Cleavagementioning

confidence: 99%

Shedding and uptake of gangliosides and glycosylphosphatidylinositol-anchored proteins

Lauc

Heffer-Lauc

2006

Biochimica et Biophysica Acta (BBA) - General Subjects

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“…3.1.3.5) or CD73 (Resta et al, 1993) is a 5Ј-monophosphoadenosine-or inosine-specific phosphatase (Zimmermann, 1992). Upon activation of phosphatidylinositol-specific phospholipase C, the GPI-anchored ecto-protein could be released in soluble form, while retaining its catalytic activity (Misumi et al, 1990;Lehto and Sharom, 1998).…”

mentioning

confidence: 99%

Enzyme Kinetics and Pharmacological Characterization of Nucleotidases Released from the Guinea Pig Isolated Vas Deferens during Nerve Stimulation: Evidence for a Soluble Ecto-Nucleoside Triphosphate Diphosphohydrolase-Like ATPase and a Soluble Ecto-5′-Nucleotidase-Like AMPase

Mihaylova-Todorova¹,

Todorov²,

Westfall³

2002

J Pharmacol Exp Ther

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Previously, we have demonstrated that stimulation of the sympathetic nerves of the guinea pig vas deferens evokes release not only of the cotransmitters ATP and norepinephrine but also of soluble nucleotidases that break down extracellular ATP, ADP, and AMP into adenosine. In this study we show that the apparent K m values of the releasable enzyme activity vary depending on which of these adenine nucleotides is used as initial substrate. The K m value for ATP was 33.6 Ϯ 2.3 M, 21.0 Ϯ 2.3 M for ADP, and 10.0 Ϯ 1.1 M for AMP. The ratios of the V max values for each enzyme reaction were 4:2:3. We have also found a different sensitivity of the metabolism of ATP and AMP by releasable nucleotidases to known nucleotidase inhibitors. Suramin inhibited the breakdown of ATP by releasable nucleotidases in a noncompetitive manner and with a K i value of 53 M, but had no effect on the breakdown of AMP. The 5Ј-nucleotidase inhibitor ␣,␤-methylene ADP inhibited the breakdown of AMP but not that of ATP. Concanavalin A inhibited the breakdown of AMP but had neither inhibitory nor facilitatory effects on the breakdown of ATP. 6-N,N-Diethyl-␤,␥-dibromomethylene-D-ATP (ARL67156), an ecto-ATPase inhibitor, suppressed ATPase and AMPase activities, whereas NaN 3 (10 mM) affected neither reaction, but inhibited the ADP metabolism. Phosphatase-and phosphodiesterase inhibitors did not affect the activity of the releasable nucleotidases. This evidence suggests that the soluble nucleotidases released during neurogenic stimulation of the guinea pig vas deferens combine an ecto-5Ј-nucleotidase-like and an ecto-nucleoside triphosphate diphosphohydrolase-like activity.ATP is released as a cotransmitter from cholinergic, adrenergic, and GABAergic neurons (Silinsky et al., 1998;Burnstock, 1999;Jo and Schlichter, 1999). Traditionally, the inactivation of neurotransmitter ATP in both the central and the peripheral nervous systems has been attributed to its breakdown by cell membrane-bound enzymes, classified as ecto-ATPases, ecto-apyrases, and ecto-5Ј-nucleotidases (Zimmermann, 1992;Plesner, 1995).We have demonstrated, however, that neurogenic stimulation of the guinea pig vas deferens dramatically accelerates the degradation of exogenous ATP (Todorov et al., 1996). The difference between the rate of degradation of extracellular ATP by tissue preparations under resting conditions and that during nerve stimulation appears to be associated with a release of enzymes that break down ATP as well as ADP and AMP into ADO (Todorov et al., 1997). Inhibition of the propagation of neuronal action potentials with tetrodotoxin, suppression of adrenergic neurotransmission with guanethidine, or inhibition of exocytosis by omission of extracellular Ca 2ϩ all prevented the release of nucleotidase activity, implying that sympathetic nerves are the source of the enzyme(s) (Todorov et al., 1997). Interestingly, the nucleotidase activity appears to be coreleased with neurotransmitter ATP and not with the sympathetic cotransmitter NE (MihaylovaTodorova et al., ...

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“…A number of GPI-anchored proteins have been shown to be released from lymphocytes by phospholipases in the serum and to exert important signaling functions in the lymphoid system [18]. Soluble PrP has been detected in serum of humans and mice, suggesting possible physiological relevance [19].…”

Section: Discussionmentioning

confidence: 99%

Expression profiles of prion and doppel proteins and of their receptors in mouse splenocytes

et al. 2008

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Doppel (Dpl) shares common structural features with the prion protein (PrP) whose pathologic isoform is considered as the causative agent of prion diseases. Although their physiological functions in the immune system remain largely unknown, we demonstrated that substantial amounts of PrP and Dpl are expressed by spleen cells notably B lymphocytes, granulocytes and DC, but not T lymphocytes and NK. To characterize transinteracting partners of PrP and Dpl on mouse splenocytes, fluorescent PrP and Dpl tetramers were produced and used as tracers. Both tetramers specifically bind to B lymphocytes, dendritic cells, macrophages and granulocytes and in a lesser extend to T lymphocytes. No binding was observed on NK, follicular dendritic cells and mesenchymal spleen cells. The activation of intracellular transduction signals (i.e. intracellular calcium concentration and activation of the MAP kinase pathway) suggested that PrP and Dpl tetramers bind to functional receptors on B cells. None of the previously described PrP partners account for the binding sites characterized here. Our study suggests a possible role for PrP and Dpl in the cell-cell interactions in the immune system.

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Release of the glycosylphosphatidylinositol-anchored enzyme ecto-5′-nucleotidase by phospholipase C: catalytic activation and modulation by the lipid bilayer

Cited by 59 publications

References 45 publications

Shedding and uptake of gangliosides and glycosylphosphatidylinositol-anchored proteins

Shedding and uptake of gangliosides and glycosylphosphatidylinositol-anchored proteins

Enzyme Kinetics and Pharmacological Characterization of Nucleotidases Released from the Guinea Pig Isolated Vas Deferens during Nerve Stimulation: Evidence for a Soluble Ecto-Nucleoside Triphosphate Diphosphohydrolase-Like ATPase and a Soluble Ecto-5′-Nucleotidase-Like AMPase

Expression profiles of prion and doppel proteins and of their receptors in mouse splenocytes

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