Comparative gene expression profiling of in vitro differentiated megakaryocytes and erythroblasts identifies novel activatory and inhibitory platelet membrane proteins

Macaulay, Iain C.; Tijssen, Marloes R.; Thijssen-Timmer, Daphne C.; Gusnanto, Arief; Steward, M. W.; Burns, Philippa; Langford, Cordelia; Ellis, Peter; Dudbridge, Frank; Zwaginga, Jaap‐Jan; Watkins, Nicholas A.; Schoot, C. Ellen van der; Ouwehand, Willem H.

doi:10.1182/blood-2006-07-036269

Cited by 151 publications

(155 citation statements)

References 62 publications

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“…Interestingly this pathway is known to be activated by G i in cardiac myocytes and its inhibition to convert survival to apoptotic signaling (Zhu et al, 2001). (Rubic et aL, 2008) ERK1/2 phosphorylation ↑ TNF-α, IL-1β and cytokines (Rubic et al, 2008) iDC migration Platelet (Macaulay et al, 2007) ↓ cAMP and Src kinase activation via G i PI3K activation, Akt phosphorylation via βγ Pselectin and glycoprotein (GP)IIb-IIIa activation (Hogberg et al, 2011 ) Crosstalk with other GPCRs (ADP, TXA2) (Spath et al, 2012) ↓ platelet aggregation (Macaulay et al, 2007;Spath et al, 2012) (Potentiation of (Spath et al, 2012)) platelet aggregation (Hogberg et al, 2011) Inhibition of antiplatelets Monocytes T and B (Rubic et al, 2008) ↑ TNFα and IFN--γ (Rubic et al, 2008) Immunity (Rubic et al, 2008) …”

Section: Hypertensionmentioning

confidence: 99%

“…The precise mechanism of this effect remains unknown, but has been rediscovered and investigated more recently (Hogberg et al, 2011;Macaulay et al, 2007;Spath, Hansen, Bokemeyer, & Langer, 2012).…”

Section: Platelet Physiologymentioning

confidence: 99%

“…SUCNR1 is expressed in megakaryocytes at both protein and mRNA levels (Hakak et al, 2009;Macaulay et al, 2007). SUCNR1 is expressed in hematopoietic progenitor cells (HPC) of the bone marrow.…”

Section: Platelet Physiologymentioning

confidence: 99%

“…In addition, SUCNR1 has been identified as one of the most highly expressed GPCRs in human platelets, at a level corresponding to the P2Y 1 receptor, indicating a potential important role in platelet physiology (Amisten et al, 2008 ;Hogberg et al, 2011 ;Macaulay et al, 2007 ;Spath et al, 2012).…”

Section: Platelet Physiologymentioning

confidence: 99%

“…In humans, SUCNR1 protein was identified at the surface of T (CD4+, CD8+) and B (CD19+) cells as well as monocytes (CD14+) (Macaulay et al, 2007). At the mRNA level, SUCNR1 was also detected in macrophages and iDC (Rubic et al, 2008).…”

Section: Immune System and Inflammationmentioning

confidence: 99%

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Insight into SUCNR1 (GPR91) structure and function

Gilissen

Jouret

Pirotte

et al. 2016

Pharmacology & Therapeutics

111

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SUCNR1 (or GPR91) belongs to the family of G protein-coupled receptors (GPCR), which represents the largest group of membrane proteins in human genome. The majority of marketed drugs targets GPCRs, directly or indirectly. SUCNR1 has been classified as an orphan receptor until a landmark study paired it with succinate, a citric acid cycle intermediate.According to the current paradigm, succinate triggers SUCNR1 signaling pathways to indicate local stress that may affect cellular metabolism. SUCNR1 implication has been well documented in renin-induced hypertension, ischemia/reperfusion injury, inflammation and immune response, platelet aggregation and retinal angiogenesis. In addition, the SUCNR1-induced increase of blood pressure may contribute to diabetic nephropathy or cardiac hypertrophy.The understanding of SUCNR1 activation, signaling pathways and functions remains largely elusive, which calls for deeper investigations. SUCNR1 shows a high potential as an innovative drug target and is probably an important regulator of basic physiology. In order to achieve the full characterization of this receptor, more specific pharmacological tools such as small-molecules modulators will represent an important asset. In this review, we describe the structural features of SUCNR1, its current ligands and putative binding pocket. We give an exhaustive overview of the known and hypothetical signaling partners of the receptor in different in vitro and in vivo systems. The link between SUCNR1 intracellular pathways and its pathophysiological roles are also extensively discussed.

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Section: Hypertensionmentioning

confidence: 99%

Section: Platelet Physiologymentioning

confidence: 99%

Section: Platelet Physiologymentioning

confidence: 99%

Section: Platelet Physiologymentioning

confidence: 99%

Section: Immune System and Inflammationmentioning

confidence: 99%

See 3 more Smart Citations

Insight into SUCNR1 (GPR91) structure and function

Gilissen

Jouret

Pirotte

et al. 2016

Pharmacology & Therapeutics

111

View full text Add to dashboard Cite

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The Application of Microarray Analysis and its Integration with Proteomics for Study of Platelet‐Associated Disorders

Gnatenko

Bahou

2011

Platelet Proteomics

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Systems Biology of Megakaryocytes

Kaushansky

Kaushansky²

2014

A Systems Biology Approach to Blood

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The molecular pathways that regulate megakaryocyte production have historically been identified through multiple candidate gene approaches. Several transcription factors critical for generating megakaryocytes were identified by promoter analysis of megakaryocyte-specific genes, and their biological roles then verified by gene knockout studies; for example, GATA-1, NF-E2, and RUNX1 were identified in this way. In contrast, other transcription factors important for megakaryopoiesis were discovered through a systems approach; for example, c-Myb was found to be critical for the erythroid versus megakaryocyte lineage decision by genome-wide loss-of-function studies. The regulation of the levels of these transcription factors is, for the most part, cell intrinsic, although that assumption has recently been challenged. Epigenetics also impacts megakaryocyte gene expression, mediated by histone acetylation and methylation. Several cytokines have been identified to regulate megakaryocyte survival, proliferation, and differentiation, most prominent of which is thrombopoietin. Upon binding to its receptor, the product of the c-Mpl proto-oncogene, thrombopoietin induces a conformational change that activates a number of secondary messengers that promote cell survival, proliferation, and differentiation, and down-modulate receptor signaling. Among the best studied are the signal transducers and activators of transcription (STAT) proteins; phosphoinositol-3-kinase; mitogen-activated protein kinases; the phosphatases PTEN, SHP1, SHP2, and SHIP1; and the suppressors of cytokine signaling (SOCS) proteins. Additional signals activated by these secondary mediators include mammalian target of rapamycin; β(beta)-catenin; the G proteins Rac1, Rho, and CDC42; several transcription factors, including hypoxia-inducible factor 1α(alpha), the homeobox-containing proteins HOXB4 and HOXA9, and a number of signaling mediators that are reduced, including glycogen synthase kinase 3α(alpha) and the FOXO3 family of forkhead proteins. More recently, systematic interrogation of several aspects of megakaryocyte formation have been conducted, employing genomics, proteomics, and chromatin immunoprecipitation (ChIP) analyses, among others, and have yielded many previously unappreciated signaling mechanisms that regulate megakaryocyte lineage determination, proliferation, and differentiation. This chapter focuses on these pathways in normal and neoplastic megakaryopoiesis, and suggests areas that are ripe for further study.

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Comparative gene expression profiling of in vitro differentiated megakaryocytes and erythroblasts identifies novel activatory and inhibitory platelet membrane proteins

Cited by 151 publications

References 62 publications

Insight into SUCNR1 (GPR91) structure and function

Insight into SUCNR1 (GPR91) structure and function

The Application of Microarray Analysis and its Integration with Proteomics for Study of Platelet‐Associated Disorders

Systems Biology of Megakaryocytes

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