Identification of a Mammalian Angiopoietin-Related Protein Expressed Specifically in Liver

Conklin, Darrell; Gilbertson, Debra G.; Taft, David W.; Maurer, Mark; Whitmore, Theodore E.; Smith, Deborah L.; Walker, Kathleen M.; Chen, Lennie H.; Wattler, Sigrid; Nehls, Michael; Lewis, Kenneth B.

doi:10.1006/geno.1999.6041

Cited by 147 publications

(121 citation statements)

References 18 publications

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“…The result is similar to studies in Chinese Holstein cattle (Guan et al, 2010), pigs (Xia et al, 2006), goats , mice (Conklin et al, 1999a) and humans (Kersten and Bensadoun, 2009). The similar structure of ANGPTL3 between cow and other species indicated that ANGPTL3 might have similar functions among various species.…”

Section: Discussionsupporting

confidence: 89%

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Tissue expression and predicted protein structures of the bovine ANGPTL3 and association of novel SNPs with growth and meat quality traits

Chen

Yang

et al. 2015

Animal

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Angiopoietin-like protein 3 (ANGPTL3) is a secreted protein that regulates lipid, glucose and energy metabolism. This study was conducted to better understand the effect of ANGPTL3 on important economic traits in cattle. First, transcript profiles for ANGPTL3 were measured in nine different Jiaxian cattle tissues. Second, polymorphisms were identified in the complete coding region and promoter region of the bovine ANGPTL3 gene in 707 cattle samples. Finally, an association study was carried out utilizing these single nucleotide polymorphisms (SNPs) to determine the effect of these SNPs on the growth and meat quality traits. Quantitative real-time PCR analysis showed that ANGPTL3 was mainly expressed in the liver. The promoter of the bovine ANGPTL3 contained several putative transcription factor binding sites (SF1, HNF-1, LXRα, NFκβ, HNF-3 and C/EBP). In total, four SNPs of the bovine ANGPTL3 gene were identified by direct sequencing. SNP1 (rs469906272: g. − 38T > C) was identified in the promoter, SNP2 (rs451104723:g.104A > T) and SNP3 (rs482516226: g.509A > G) were identified in exon 1, and SNP4 (rs477165942: g.8661T > C) was identified in exon 6. Changes in predicted protein structures due to non-synonymous SNPs were analyzed. Haplotype frequencies and linkage disequilibrium were also investigated. Analysis of four SNPs in cattle from different native Chinese breeds (Nanyang (NY) and Jiaxian (JX)) and commercial breeds (Angus (AG), Hereford (HF), Limousin (LM), Luxi (LX), Simmental (ST) and Jinnan (JN)) revealed a significant association with growth traits (including: BW and hipbone width) and meat quality traits (including: Warner-Bratzler shear force and ribeye area). Therefore, implementation of these four mutations in selection indices in the beef industry may be beneficial in selecting individuals with superior growth and meat quality traits.

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Section: Discussionsupporting

confidence: 89%

“…ANGPTL3 is a liver secreted protein encoded by the ANGPTL3 gene (Conklin et al, 1999b). ANGPTL3 plays a key role in lipid metabolism by increasing plasma lipids and high-density lipoprotein cholesterol (HDL-C) through the inhibition of lipoprotein lipase (Foka et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Tissue expression and predicted protein structures of the bovine ANGPTL3 and association of novel SNPs with growth and meat quality traits

Chen

Yang

et al. 2015

Animal

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“…Distinct from Tie1 or Tie2-The sequences for both human and mouse ANGPTL3 have been published previously (14). In analogy to the angiopoietins, ANGPTL3 is a secreted factor consisting of an N-terminal signal peptide, followed by a coiled-coil domain and a C-terminal FBN-like domain (Fig.…”

Section: Angptl3 Binds To Endothelial Cells Via Receptorsmentioning

confidence: 99%

ANGPTL3 Stimulates Endothelial Cell Adhesion and Migration via Integrin αvβ3 and Induces Blood Vessel Formation in Vivo

Camenisch¹,

Pisabarro²,

Sherman³

et al. 2002

Journal of Biological Chemistry

216

209

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The angiopoietin family of secreted factors is functionally defined by the C-terminal fibrinogen (FBN)-like domain, which mediates binding to the Tie2 receptor and thereby facilitates a cascade of events ultimately regulating blood vessel formation. By screening expressed sequence tag data bases for homologies to a consensus FBN-like motive, we have identified ANGPTL3, a liver-specific, secreted factor consisting of an N-terminal coiled-coil domain and the C-terminal FBN-like domain. Co-immunoprecipitation experiments, however, failed to detect binding of ANGPTL3 to the Tie2 receptor. A molecular model of the FBN-like domain of ANGPTL3 was generated and predicted potential binding to integrins. This hypothesis was experimentally confirmed by the finding that recombinant ANGPTL3 bound to ␣ v ␤ 3 and induced integrin ␣ v ␤ 3 -dependent haptotactic endothelial cell adhesion and migration and stimulated signal transduction pathways characteristic for integrin activation, including phosphorylation of Akt, mitogen-activated protein kinase, and focal adhesion kinase. When tested in the rat corneal assay, ANGPTL3 strongly induced angiogenesis with comparable magnitude as observed for vascular endothelial growth factor-A. Moreover, the C-terminal FBN-like domain alone was sufficient to induce endothelial cell adhesion and in vivo angiogenesis. Taken together, our data demonstrate that ANGPTL3 is the first member of the angiopoietin-like family of secreted factors binding to integrin ␣ v ␤ 3 and suggest a possible role in the regulation of angiogenesis.

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“…Genetic analysis and positional cloning in the KK/San mice identified a 4-bp nucleotide insertion in exon 6 of the gene encoding angiopoietin-like protein 3 (Angptl3), 1 which caused a premature termination after frameshift (4). Angptl3 is a ϳ70-kDa secretory protein, and its mRNA is expressed exclusively in the livers of humans and mice (5). The protein contains a coiled-coil region and fibrinogen-like motif and shows similarity in amino acid sequence and structure with angiopoietin (5).…”

mentioning

confidence: 99%

“…Angptl3 is a ϳ70-kDa secretory protein, and its mRNA is expressed exclusively in the livers of humans and mice (5). The protein contains a coiled-coil region and fibrinogen-like motif and shows similarity in amino acid sequence and structure with angiopoietin (5). Angptl3 can also induce angioneogenesis at a lesser degree than angiopoietin (6).…”

mentioning

confidence: 99%

Angiopoietin-like Protein 3 Mediates Hypertriglyceridemia Induced by the Liver X Receptor

Inaba

Matsuda

Shimamura

et al. 2003

Journal of Biological Chemistry

127

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The KK/San obese and diabetic mouse, a mutant strain from KK obese mice, exhibits significantly low plasma triglyceride levels. In KK/San mice, genetic analysis identified a mutation in the gene encoding angiopoietinlike protein 3 (Angptl3), a liver-specific secretory protein, which had suppressive effect on lipoprotein lipase activity. In the current study, LXR ligands augmented Angptl3 mRNA expression and protein production in hepatoma cells. LXR ligands and LXR⅐retinoid X receptor (RXR) complex increased the promoter activity of Angptl3 gene. Serial deletion and point mutation of Angptl3 promoter identified an LXR response element (LXRE). Gel mobility shift assay showed the direct binding of LXR⅐RXR complex to the LXRE of the Angptl3 promoter. Furthermore, treatment of mice with synthetic LXR ligand caused triglyceride accumulation in the liver and plasma, which was accompanied by induction of hepatic mRNAs of several LXR target genes, including sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and Angptl3. In Angptl3-deficient C57BL/6J mice, LXR ligand did not cause hypertriglyceridemia but accumulation of triglyceride in the liver. Our results demonstrate that Angptl3 is a direct target of LXR and that induction of hepatic Angptl3 accounts for hypertriglyceridemia associated with the treatment of LXR ligand.

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Identification of a Mammalian Angiopoietin-Related Protein Expressed Specifically in Liver

Cited by 147 publications

References 18 publications

Tissue expression and predicted protein structures of the bovine ANGPTL3 and association of novel SNPs with growth and meat quality traits

Tissue expression and predicted protein structures of the bovine ANGPTL3 and association of novel SNPs with growth and meat quality traits

ANGPTL3 Stimulates Endothelial Cell Adhesion and Migration via Integrin αvβ3 and Induces Blood Vessel Formation in Vivo

Angiopoietin-like Protein 3 Mediates Hypertriglyceridemia Induced by the Liver X Receptor

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