Isolation and Characterization of a Novel Endogenous Peptide Ligand for the Human APJ Receptor

Tatemoto, Kazuhiko; Hashimoto, Masaki; Habata, Yugo; Fujii, Ryo; Kakegawa, Tadao; Zou, Min‐Xu; Kawamata, Yuji; Fukusumi, Shoji; Hinuma, Shuji; Kitada, Chieko; Kurokawa, Tsutomu; Onda, Haruo; Fujino, Masahiko

doi:10.1006/bbrc.1998.9489

Cited by 1,453 publications

(1,210 citation statements)

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“…The existence of the apelinergic system began to unfold in 1998 when APJ (angiotensin II receptor-like 1), a formerly orphan Gprotein coupled receptor (GPCR), and its ligand were finally paired by Tatemoto et al [45]. Apelin was identified as an endogenous ligand for APJ receptor.…”

Section: Introductionmentioning

confidence: 99%

“…This peptide is translated as a 77-amino acid precursor, which undergoes proteolytic maturation generating shorter active apelin peptides. Apelin-36 was the first of these shorter C-terminal sequences being described to bind and activate APJ [45]. Also Apelin-17, Apelin-13 and its pyroglutamyl isoform which is resistant to degradation, (Pyr1)-Apelin-13, were proven to act as functional ligands of APJ and in some cases exhibited much higher biological activity than Apelin-36 [45,17,18,25,46].…”

Section: Introductionmentioning

confidence: 99%

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The apelinergic system in the developing lung: Expression and signaling

et al. 2011

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a b s t r a c tApelin and its receptor APJ constitute a signaling pathway best recognized as an important regulator of cardiovascular homeostasis. This multifunctional peptidergic system is currently being described to be involved in embryonic events which extend into vascular, ocular and heart development. Additionally, it is highly expressed in pulmonary tissue. Therefore, the aim of this study was to investigate the role of apelinergic system during fetal lung development. Immunohistochemistry and Western blot analysis were used to characterize apelin and APJ expression levels and cellular localization in normal fetal rat lungs, at five different gestational ages as well as in the adult. Fetal rat lung explants were cultured in vitro with increasing doses of apelin. Treated lung explants were morphometrically analyzed and assessed for MAPK signaling modifications. Both components of the apelinergic system are constitutively expressed in the developing lung, with APJ exhibiting monomeric, dimeric and oligomeric forms in the pulmonary tissue. Pulmonary epithelium also displayed constitutive nuclear localization of the receptor. Fetal apelin expression is higher than adult expression. Apelin supplementation inhibitory effect on branching morphogenesis was associated with a dose dependent decrease in p38 and JNK phosphorylation. The results presented provide the first evidence of the presence of an apelinergic system operating in the developing lung. Our findings also suggest that apelin inhibits fetal lung growth by suppressing p38 and JNK signaling pathways.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The apelinergic system in the developing lung: Expression and signaling

et al. 2011

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“…Apelin (stomach). Apelin is a peptide isolated from extracts of the bovine stomach (Tatemoto et al, 1998). It has been identified as the endogenous ligand of the human orphan, APJ receptor (Tatemoto et al, 1998).…”

Section: Metabolic Hormonesmentioning

confidence: 99%

“…Apelin is a peptide isolated from extracts of the bovine stomach (Tatemoto et al, 1998). It has been identified as the endogenous ligand of the human orphan, APJ receptor (Tatemoto et al, 1998). Apelin is derived from a larger precursor, preproapelin, the cDNA for which has been cloned in humans, cattle, rats and mice (Tatemoto et al, 1998).…”

Section: Metabolic Hormonesmentioning

confidence: 99%

“…It has been identified as the endogenous ligand of the human orphan, APJ receptor (Tatemoto et al, 1998). Apelin is derived from a larger precursor, preproapelin, the cDNA for which has been cloned in humans, cattle, rats and mice (Tatemoto et al, 1998). Plasma apelin is upregulated in rodents and humans during obesity, there is a strong relationship between adipocyte-secreted apelin and insulin levels (Boucher et al, 2005).…”

Section: Metabolic Hormonesmentioning

confidence: 99%

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The effect of nutrition and metabolic status on the development of follicles, oocytes and embryos in ruminants

Dupont

Scaramuzzi

Reverchon

2014

animal

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The impact of nutrition and energy reserves on the fertility of ruminants has been extensively described. However, the metabolic factors and the molecular mechanisms involved in the interactions between nutrition and ovarian function are still poorly understood. These factors could be hormonal (either reproductive and/or metabolic) and/or dietary and metabolic (glucose, amino acids and fatty acids). In this review, we briefly summarize the impact of those nutrients (fatty acids, glucose and amino acids) and metabolic hormones (insulin/IGF-I, growth hormone, T3/4, ghrelin, apelin and the adipokines (leptin, adiponectin and resistin)) implicated in the development of ovarian follicles, oocytes and embryos in ruminants. We then discuss the current hypotheses on the mechanisms of action of these factors on ovarian function. We particularly describe the role of some energy sensors including adenosine monophosphate-activated kinase and peroxisome proliferator-activated receptors in the ovarian cells.

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Molecular determinants on extracellular loop domains that dictate interaction between β‐arrestin and human APJ receptor

2019

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The human APJ receptor (APJR), activated by apelin isoforms, regulates cardiovascular functions and fluid homeostasis. Understanding its structure‐function relationship is crucial for a comprehensive knowledge of signalling aberrations that cause several physiological disorders. Here, we demonstrate the influence of extracellular loop (ECL) domains in the mechanism of β‐arrestin‐mediated signalling from human APJR: Apelin system. Alanine mutations of evolutionarily conserved residues were characterized using receptor internalization, β‐arrestin pull‐down, Akt phosphorylation and cell migration assay. C281A and 268KTL270‐AAA in ECL3 were deficient in all assays, whereas 183MDYS186‐AAAA mutant in ECL2 showed impaired β‐arrestin‐mediated signalling but demonstrated Gi‐dependent cell migration. Our findings establish that conserved residues in the extracellular domain play a prominent role in modulating receptor interactions with the β‐arrestin signalling cascade.

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Isolation and Characterization of a Novel Endogenous Peptide Ligand for the Human APJ Receptor

Cited by 1,453 publications

References 13 publications

The apelinergic system in the developing lung: Expression and signaling

The apelinergic system in the developing lung: Expression and signaling

The effect of nutrition and metabolic status on the development of follicles, oocytes and embryos in ruminants

Molecular determinants on extracellular loop domains that dictate interaction between β‐arrestin and human APJ receptor

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