G-protein-coupled receptors in normal human erythroid progenitor cells

Porzig, H.; Gutknecht, Regula; Kostova, G.; Thalmeier, K

doi:10.1007/bf00168910

Cited by 18 publications

(11 citation statements)

References 57 publications

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“…cAMP levels rise late in differentiation. Erythroid cells express G␣ s -coupled receptors, among which are the adrenergic receptor and receptors for thrombin and PGE2 (56). Notably, the PGE2 receptor is upregulated late in differentiation (W. J. Bakker and M. von Lindern, unpublished data; 25), whereas prostaglandin dehydrogenase (Pgdh1) is induced by dexamethasone in expanding erythroblasts and rapidly downregulated during differentiation (42; Bakker and von Lindern, unpublished).…”

Section: Vol 27 2007 Foxo3a Target Genes In Erythropoiesis 3851mentioning

confidence: 99%

Differential Regulation of Foxo3a Target Genes in Erythropoiesis

Bakker

Dijk

Amelsvoort

et al. 2007

Molecular and Cellular Biology

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The cooperation of stem cell factor (SCF) and erythropoietin (Epo) is required to induce renewal divisions in erythroid progenitors, whereas differentiation to mature erythrocytes requires the presence of Epo only. Epo and SCF activate common signaling pathways such as the activation of protein kinase B (PKB) and the subsequent phosphorylation and inactivation of Foxo3a. In contrast, only Epo activates Stat5. Both Foxo3a and Stat5 promote erythroid differentiation. To understand the interplay of SCF and Epo in maintaining the balance between renewal and differentiation during erythroid development, we investigated differential Foxo3a target regulation by Epo and SCF. Expression profiling revealed that a subset of Foxo3a targets was not inhibited but was activated by Epo. One of these genes was Cited2. Transcriptional control of Epo/Foxo3a-induced Cited2 was studied and compared with that of the Epo-repressed Foxo3a target Btg1. We show that in response to Epo, the allegedly growth-inhibitory factor Foxo3a associates with the allegedly growth-stimulatory factor Stat5 in the nucleus, which is required for Epo-induced Cited2 expression. In contrast, Btg1 expression is controlled by the cooperation of Foxo3a with cyclic AMP-and Jun kinase-dependent Creb family members. Thus, Foxo3a not only is an effector of PKB but also integrates distinct signals to regulate gene expression in erythropoiesis.

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Section: Vol 27 2007 Foxo3a Target Genes In Erythropoiesis 3851mentioning

confidence: 99%

Differential Regulation of Foxo3a Target Genes in Erythropoiesis

Bakker

Dijk

Amelsvoort

et al. 2007

Molecular and Cellular Biology

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“…It is also possible that PKC, together with tyrosine kinases complementing JAK2, is required to maintain a signaling structure, the so-called "signalosome." Therefore, potential scaffolding proteins containing multiple protein-protein interaction domains like the PDZ domain also must be considered as potential targets for PKC (67,68).…”

Section: Figmentioning

confidence: 99%

Protein Kinase C α Controls Erythropoietin Receptor Signaling

Lindern¹,

Amelsvoort²,

Dijk³

et al. 2000

Journal of Biological Chemistry

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Protein kinase C (PKC) is implied in the activation of multiple targets of erythropoietin (Epo) signaling, but its exact role in Epo receptor (EpoR) signal transduction and in the regulation of erythroid proliferation and differentiation remained elusive. We analyzed the effect of PKC inhibitors with distinct modes of action on EpoR signaling in primary human erythroblasts and in a recently established murine erythroid cell line. Active PKC appeared essential for Epo-induced phosphorylation of the Epo receptor itself, STAT5, Gab1, Erk1/2, AKT, and other downstream targets. Under the same conditions, stem cell factor-induced signal transduction was not impaired. LY294002, a specific inhibitor of phosphoinositol 3-kinase, also suppressed Epo-induced signal transduction, which could be partially relieved by activators of PKC. PKC inhibitors or LY294002 did not affect membrane expression of the EpoR, the association of JAK2 with the EpoR, or the in vitro kinase activity of JAK2. The data suggest that PKC controls EpoR signaling instead of being a downstream effector. PKC and phosphoinositol 3-kinase may act in concert to regulate association of the EpoR complex such that it is responsive to ligand stimulation. Reduced PKC-activity inhibited Epo-dependent differentiation, although it did not effect Epo-dependent "renewal divisions" induced in the presence of Epo, stem cell factor, and dexamethasone.

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“…Suppression-In addition to activating an effector system directly, receptor-mediated stimulation of hematopoietic cells may also result in potentiating the action of a second ligand that is administered simultaneously with, or subsequently to, the primary agonist (31,37,38). Thus, the stimulation of HEL cells with UTP (100 M) prior to challenging with PGE 1 substantially enhanced the mobilization of intracellular Ca 2ϩ by the second agonist (Fig.…”

Section: Utp Generates a Potentiating Effect On Pge 1 -Induced Changementioning

confidence: 99%

The P2U Purinoceptor Obligatorily Engages the Heterotrimeric G Protein G16 to Mobilize Intracellular Ca2+ in Human Erythroleukemia Cells

Baltensperger

Porzig

1997

Journal of Biological Chemistry

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To assess the role of G 16 , a trimeric G protein exclusively expressed in hematopoietic cells, G ␣16 antisense RNA was stably expressed in human erythroleukemia (HEL) cells. Western blot analysis showed that in transfected cell lines, the expression of endogenous G ␣16 protein was suppressed, but the expression of G ␣q/11 , G ␣i2 , and G ␣i3 remained unaffected. Suppression of G ␣16 in transfected HEL cells did not interfere with transient elevations of intracellular free Ca 2؉ concentrations induced by prostaglandin E 1 (PGE 1 ), platelet-activating factor, or thrombin. In parental HEL cells, UTP and ATP mobilized Ca 2؉ from intracellular stores with half-maximum effective concentrations of 3.6 ؎ 0.7 and 4.7 ؎ 1.6 M, respectively, apparently by stimulating P 2U purinoceptors. By contrast, Ca 2؉ mobilization by UTP or ATP was completely abrogated in G ␣16 -suppressed cells, indicating specific coupling of G 16 to P 2U purinoceptors. Pertussis toxin inhibited the effect of UTP in parental HEL cells by 57.6 ؎ 4.9%. These data indicate that signaling by the P 2U purinoceptor obligatorily requires G 16 but may be modulated further by activation of G i . Priming of HEL cells with UTP or ATP prior to stimulation with PGE 1 markedly enhanced the PGE 1 -induced intracellular Ca 2؉ release. This indirect, potentiating effect of UTP and ATP was not impaired in G ␣16 -suppressed cells but was inhibited by pertussis toxin, indicating that functional P 2U purinoceptors are present on these cells and that the potentiating effect primarily depends on G i . The data demonstrate (i) that G ␣16 antisense RNA selectively inhibits endogenous G ␣16 protein expression in HEL cells; (ii) that stimulation of endogenous P 2U (P2Y 2 ) purinoceptors leads to the mobilization of intracellular Ca 2؉ by a mechanism that strictly depends on G ␣16 ; and (iii) that P 2U purinoceptors in HEL cells can communicate with two distinct signaling pathways diverging at the G protein level.

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G-protein-coupled receptors in normal human erythroid progenitor cells

Cited by 18 publications

References 57 publications

Differential Regulation of Foxo3a Target Genes in Erythropoiesis

Differential Regulation of Foxo3a Target Genes in Erythropoiesis

Protein Kinase C α Controls Erythropoietin Receptor Signaling

The P2U Purinoceptor Obligatorily Engages the Heterotrimeric G Protein G16 to Mobilize Intracellular Ca2+ in Human Erythroleukemia Cells

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