Involvement of deoxygenation-induced increase in tyrosine kinase activity in sickle cell dehydration

Merciris, Patrick; Hardy‐Dessources, Marie‐Dominique; Sauvage, M.; Giraud, Françoise

doi:10.1007/s004240050638

Cited by 21 publications

(18 citation statements)

References 38 publications

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“…1 In a previous study, to characterize the cell signaling events that lead to the dehydration of deoxygenated SS cells, we have shown that deoxygenation increased protein tyrosine kinase (PTK) activity and that PTK inhibitors reduced SS cell dehydration by decreasing the K ϩ loss either in the presence or absence of Ca ϩϩ in the medium without affecting SIP. 2 These data provide evidence that either one or both K ϩ transporters might be regulated by a pathway implicating a tyrosine phosphorylation. Unlike in SS cells, PTK activity in normal red cells (AA cells) was not affected by deoxygenation.…”

Section: Introductionmentioning

confidence: 82%

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

Merciris

Hardy‐Dessources

Giraud

2001

Blood

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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 deoxy-genation of normal red cells, and stimulation was partly reversible on reoxygen-ation of sickle cells. Syk activation was independent of the increase in intracellu-lar Ca and Mg 2 associated with deoxy-genation. Lectins that promote glyco-phorin 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 auto-phosphorylation. 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. (Blood. 2001;98:3121-3127)

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Section: Introductionmentioning

confidence: 82%

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

Merciris

Hardy‐Dessources

Giraud

2001

Blood

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“…As reported by us and by others, 10,11,19,[35][36][37][38]40,42 malarial parasite invasion, shrinkage of the erythrocyte in response to hypertonic stress, and exposure of the cell to oxidative stresses such as those that derive from hemoglobin denaturation/hemichrome formation, thalassemias, sickle cell disease, glucose-6-phosphate dehydrogenase, other antioxidant deficiencies, and natural aging all lead to enhanced band 3 tyrosine phosphorylation. 22,23,26 Among these stimuli, oxidative stress appears to be the most proficient, and indeed recent data demonstrate that oxidative cross-linking of band 3 directly induces its association with Syk, which in turn triggers phosphorylation of tyrosines within its cytoplasmic domain. 20 Consistent with these findings, only the oxidized fraction of band 3 becomes phosphorylated after imposition of an oxidant stress.…”

Section: Regulation Of Membrane-cytoskeletal Interaction 6003mentioning

confidence: 99%

“…20,21 In response to physiologic stimuli such as hypertonic conditions or oxidative stress, and in severe hematologic disorders such as thalassemias, sickle cell anemia, and glucose-6-phosphate dehydrogenase deficiency, 22,23 phosphorylation of band 3 on tyrosine residues can increase by several orders of magnitude. 20,[22][23][24][25][26] Although the protein tyrosine kinase Lyn has been shown to participate in this phosphorylation, 21 the protein tyrosine kinase Syk can be argued to play the more prominent role, because it has been reported to phosphorylate tyrosines 8 and 21 of band 3, 20 which in turn generates a binding site for other protein tyrosine kinases. 21 Of more direct relevance to erythrocyte signal transduction, Syk may also mediate the effects of oxidant stress on band 3 tyrosine phosphorylation, because it strongly prefers to phosphorylate a reversibly oxidized conformation of AE1.…”

Section: Introductionmentioning

confidence: 99%

Regulation of membrane-cytoskeletal interactions by tyrosine phosphorylation of erythrocyte band 3

Ferru

Giger²,

Pantaleo

et al. 2011

Blood

174

216

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The cytoplasmic domain of band 3 serves as a center of erythrocyte membrane organization and constitutes the major substrate of erythrocyte tyrosine kinases. Tyrosine phosphorylation of band 3 is induced by several physiologic stimuli, including malaria parasite invasion, cell shrinkage, normal cell aging, and oxidant stress (thalassemias, sickle cell disease, glucose-6-phosphate dehydrogenase deficiency, etc). In an effort to characterize the biologic sequelae of band 3 tyrosine phosphorylation, we looked for changes in the polypeptide's function that accompany its phosphorylation. We report that tyrosine phosphorylation promotes dissociation of band 3 from the spectrin-actin skeleton as evidenced by: (1) a decrease in ankyrin affinity in direct binding studies, (2) an increase in detergent extractability of band 3 from ghosts, (3) a rise in band 3 cross-linkability by bis-sulfosuccinimidylsuberate, (4) significant changes in erythrocyte morphology, and (5) elevation of the rate of band 3 diffusion in intact cells. Because release of band 3 from its ankyrin and adducin linkages to the cytoskeleton can facilitate changes in multiple membrane properties, tyrosine phosphorylation of band 3 is argued to enable adaptive changes in erythrocyte biology that permit the cell to respond to the above stresses. (Blood. 2011; 117(22):5998-6006) IntroductionEarly views of the human erythrocyte argued that the cell was inert to external stimuli and that its complement of protein kinases, phospholipases, G proteins, phosphatases, and hormone receptors simply constituted nonfunctional vestiges of signaling pathways that were once operational in erythroid precursor cells. More recent evidence, however, has revealed that the human erythrocyte is highly responsive to its environment and that the cell's rich ensemble of signaling proteins likely comprise critical components in the cell's communication with its extracellular milieu. Classic hormones/signaling molecules such as prostaglandin E 2 , insulin, epinephrine, endothelin, ADP, and NO are now known to modulate erythrocyte properties in an adaptive manner, and the functional activities of many intracellular signaling intermediates have been demonstrated to regulate erythrocyte behavior. [1][2][3][4][5] One of the major targets of erythrocyte signaling appears to be the predominant membrane-spanning protein, band 3. Band 3 (AE1) catalyzes the exchange of anions (primarily HCO 3 Ϫ for Cl Ϫ ) across the erythrocyte membrane, 6 anchors the spectrin/ actin cytoskeleton to the lipid bilayer, 7 organizes and regulates a complex of glycolytic enzymes, 8,9 participates in control of erythrocyte lifespan, 10,11 nucleates several important membrane-spanning proteins, 12 and serves as a docking site for multiple peripheral membrane proteins, including protein 4.1, protein 4.2, and several kinases and phosphatases. [13][14][15][16] Not surprisingly, mutations in band 3 are frequently associated with various hemolytic diseases. 17 Perhaps because of its many important functions, band 3 is a...

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“…In sickle-cell disease, exposing the red cells to deoxygenation resulted in increased tyrosine kinase activity, concommittant with cellular dehydration. 18 Terra et al reported that the steady-state level of band 3 tyrosine phosphorylation is elevated 2-10 fold in various types of sickle cell disorder and approximately 4 fold in β-thalassemia intermedia. 19 However, tyrosine phosphorylation of β-spectrin was not documented.…”

Section: Discussionmentioning

confidence: 99%

“…It is possible that oxidative stress affects β-spectrin phosphorylation by modification of spectrin kinases/phosphatases, or by alterating the spatial arrangement of membrane proteins. [18][19][20][21][22] Reduced tyrosine kinase activity of membrane proteins is observed in Scott syndrome, a hereditary bleeding disorder characterized by a deficiency in prothrombinase activity caused by defective phospholipid scrambling activity of the blood cell membrane. 23 The decrease in membrane phospholipid scrambling results in reduction in phosphatidyl serine (PS) exposure and in prothrombinase activity on the cell surface.…”

Section: Discussionmentioning

confidence: 99%

Untitled

Tohtong¹,

Metheenukul²,

Wilairat³

2002

ScienceAsia

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The steady-state levels of β-spectrin phosphorylation in HbH (α-thalassemia 1/α-thalassemia 2), HbH/HbConstant Spring (α-thalassemia 1/HbCS, hereafter called HbH/HbCS) and nonsplenectomized β-thalassemia/HbE (hereafter called β-thal/HbE) red cells were quantitated using Western hybridization. Phosphorylation of β-spectrin serine and threonine residues from thalassemic samples was not significantly different from normal control. However, tyrosine phosphorylation was higher than normal control in HbH (p<0.01), HbH/HbCS (p<0.05) and β-thal/HbE (p<0.05) samples. Tyrosine phosphorylation of β-spectrin was observed only in the presence of vanadate, a phenomenon not hitherto reported. As tyrosine kinase activity has been linked to oxidative stress, loss of membrane lipid asymmetry and procoagulant activity of the red cell membrane, the observed increase in β-spectrin tyrosine phosphorylation of the thalassemic red cells is likely, at least in part, to account for these parameters.

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Involvement of deoxygenation-induced increase in tyrosine kinase activity in sickle cell dehydration

Cited by 21 publications

References 38 publications

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

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

Regulation of membrane-cytoskeletal interactions by tyrosine phosphorylation of erythrocyte band 3

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