Role of band 3 tyrosine phosphorylation in the regulation of erythrocyte glycolysis

Harrison, Marietta L.; Rathinavelu, Prema; Arese, Paolo; Geahlen, Robert L.; Low, Philip S.

doi:10.1016/s0021-9258(20)64292-2

Cited by 174 publications

(19 citation statements)

References 51 publications

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“…The underlying mechanism is unknown, but likely based on the overall deactivation and elimination of most kinases and/or the upregulation of phosphatase activity(ies). This process may also conserve ATP for phosphorylation of a few erythroid-specific target proteins, such as Band 3, Band 4.1, and GYPA (Boivin, 1988;Harrison, Rathinavelu et al, 1991;Manno, Takakuwa et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Integrative proteomics reveals principles of dynamic phosphosignaling networks in human erythropoiesis

Karayel

Peng

Bludau

et al. 2020

Molecular Systems Biology

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Human erythropoiesis is an exquisitely controlled multistep developmental process, and its dysregulation leads to numerous human diseases. Transcriptome and epigenome studies provided insights into system-wide regulation, but we currently lack a global mechanistic view on the dynamics of proteome and post-translational regulation coordinating erythroid maturation. We established a mass spectrometry (MS)-based proteomics workflow to quantify and dynamically track 7,400 proteins and 27,000 phosphorylation sites of five distinct maturation stages of in vitro reconstituted erythropoiesis of CD34 + HSPCs. Our data reveal developmental regulation through drastic proteome remodeling across stages of erythroid maturation encompassing most protein classes. This includes various orchestrated changes in solute carriers indicating adjustments to altered metabolic requirements. To define the distinct proteome of each maturation stage, we developed a computational deconvolution approach which revealed stagespecific marker proteins. The dynamic phosphoproteomes combined with a kinome-targeted CRISPR/Cas9 screen uncovered coordinated networks of erythropoietic kinases and pinpointed downregulation of c-Kit/MAPK signaling axis as key driver of maturation. Our system-wide view establishes the functional dynamic of complex phosphosignaling networks and regulation through proteome remodeling in erythropoiesis.

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Section: Discussionmentioning

confidence: 99%

Integrative proteomics reveals principles of dynamic phosphosignaling networks in human erythropoiesis

Karayel

Peng

Bludau

et al. 2020

Molecular Systems Biology

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“…A probable connection between thiol status and transport is tyrosine phosphorylation (363,376). Sites of tyrosine phosphorylation on band 3 include Y8 and Y21 near the NH 2 terminus; Y359 in the linker between membrane and cytoplasmic domains; and Y904 near the COOH terminus (377)(378)(379)(380). There is evidence for a role of Y359 and Y904 phosphorylation in kAE1 trafficking (381,382), but neither is necessary for anion transport; band 3 can be cleaved by trypsin adjacent to Y359 without major effect on transport (184,185), and transport is normal in band 3 Walton, which is missing residues 901-911 (381).…”

Section: Effects Of Oxidative Stress Thiol Status and Tyrosine Phosphorylationmentioning

confidence: 99%

Cell physiology and molecular mechanism of anion transport by erythrocyte band 3/AE1

Jennings

2021

American Journal of Physiology-Cell Physiology

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The major transmembrane protein of the red blood cell, known as band 3, AE1, and SLC4A1, has two main functions: 1) catalysis of Cl-/HCO3- exchange, one of the steps in CO2 excretion; 2) anchoring the membrane skeleton. This review summarizes the 150 year history of research on red cell anion transport and band 3 as an experimental system for studying membrane protein structure and ion transport mechanisms. Important early findings were that red cell Cl- transport is a tightly coupled 1:1 exchange and band 3 is labeled by stilbenesulfonate derivatives that inhibit anion transport. Biochemical studies showed that the protein is dimeric or tetrameric (paired dimers) and that there is one stilbenedisulfonate binding site per subunit of the dimer. Transport kinetics and inhibitor characteristics supported the idea that the transporter acts by an alternating access mechanism with intrinsic asymmetry. The sequence of band 3 cDNA provided a framework for detailed study of protein topology and amino acid residues important for transport. The identification of genetic variants produced insights into the roles of band 3 in red cell abnormalities and distal renal tubular acidosis. The publication of the membrane domain crystal structure made it possible to propose concrete molecular models of transport. Future research directions include improving our understanding of the transport mechanism at the molecular level and of the integrative relationships among band 3, hemoglobin, carbonic anhydrase, and gradients (both transmembrane and subcellular) of HCO3-, Cl-, O2, CO2, pH, and NO metabolites during pulmonary and systemic capillary gas exchange.

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“…Specifically, during RBC circulatory transit, binding/release of EMP enzymes to cdB3 oscillates with pO 2 , as a function of Hb conformation [5][6][7][8] and cdB3 phosphorylation status. [9][10][11][12] Notably, binding results in partial EMP enzyme inactivation, and a relative HMP flux increase in oxygenated (R-state Hb) RBCs, as a result of reduced competition for G6P substrate. EMP and HMP pathways furnish RBCs with different byproducts, thus allocating energy to RBC metabolic tasks or threats that differ between arterial (antioxidant systems) and venous (metHb reduction and ATP restoration) phases of circulatory transit.…”

Section: Introductionmentioning

confidence: 99%

Quantifying dynamic range in red blood cell energetics: Evidence of progressive energy failure during storage

Rogers

Brummet

et al. 2021

Transfusion

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Background During storage, red blood cells (RBCs) undergo significant biochemical and morphologic changes, referred to collectively as the “storage lesion”. It was hypothesized that these defects may arise from disrupted oxygen‐based regulation of RBC energy metabolism, with resultant depowering of intrinsic antioxidant systems. Study Design and Methods As a function of storage duration, the dynamic range in RBC metabolic response to three models of biochemical oxidant stress (methylene blue, hypoxanthine/xanthine oxidase, and diamide) was assessed, comparing glycolytic flux by NMR and UHPLC–MS methodologies. Blood was processed/stored under standard conditions (AS‐1 additive solution) with leukoreduction. Over a 6‐week period, RBC metabolic and antioxidant status were assessed at baseline and following exposure to the three biochemical oxidant models. Comparison was made of glycolytic flux (1H‐NMR tracking of [2‐13C]‐glucose and metabolomic phenotyping with [1,2,3‐13C3] glucose), reducing equivalent (NADPH/NADP+) recycling, and thiol‐based (GSH/GSSG) antioxidant status. Results As a function of storage duration, we observed the following: (1) a reduction in baseline hexose monophosphate pathway (HMP) flux, the sole pathway responsible for the regeneration of the essential reducing equivalent NADPH; with (2) diminished stress‐based dynamic range in both overall glycolytic as well as proportional HMP flux. In addition, progressive with storage duration, RBCs showed (3) constraint in reducing equivalent (NADPH) recycling capacity, (4) loss of thiol based (GSH) recycling capacity, and (5) dysregulation of metabolon assembly at the cytoplasmic domain of Band 3 membrane protein (cdB3). Conclusion Blood storage disturbs normal RBC metabolic control, depowering antioxidant capacity and enhancing vulnerability to oxidative injury.

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Role of band 3 tyrosine phosphorylation in the regulation of erythrocyte glycolysis

Cited by 174 publications

References 51 publications

Integrative proteomics reveals principles of dynamic phosphosignaling networks in human erythropoiesis

Integrative proteomics reveals principles of dynamic phosphosignaling networks in human erythropoiesis

Cell physiology and molecular mechanism of anion transport by erythrocyte band 3/AE1

Quantifying dynamic range in red blood cell energetics: Evidence of progressive energy failure during storage

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