Angiopoietin-related protein 3

Definition:

Acts in part as a hepatokine that is involved in regulation of lipid and glucose metabolism. Proposed to play a role in the trafficking of energy substrates to either storage or oxidative tissues in response to food intake (By similarity). Has a stimulatory effect on plasma triglycerides (TG), which is achieved by suppressing plasma TG clearance via inhibition of LPL activity. The inhibition of LPL activity appears to be an indirect mechanism involving recruitment of proprotein convertases PCSK6 and FURIN to LPL leading to cleavage and dissociation of LPL from the cell surface; the function does not require ANGPTL3 proteolytic cleavage but seems to be mediated by the N-terminal domain, and is not inhibited by GPIHBP1. Can inhibit endothelial lipase, causing increased plasma levels of high density lipoprotein (HDL) cholesterol and phospholipids. Can bind to adipocytes to activate lipolysis, releasing free fatty acids and glycerol. Suppresses LPL specifically in oxidative tissues which is required to route very low density lipoprotein (VLDL)-TG to white adipose tissue (WAT) for storage in response to food; the function may involve cooperation with circulating, liver-derived ANGPTL8 and ANGPTL4 expression in WAT (By similarity). Contributes to lower plasma levels of low density lipoprotein (LDL)-cholesterol by a mechanism that is independent of the canonical pathway implicating APOE and LDLR. May stimulate hypothalamic LPL activity (By similarity).; [ANGPTL3(17-221)]: In vitro inhibits LPL activity; not effective on GPIHBP1-stabilized LPL.; Involved in angiogenesis. Binds to endothelial cells via integrin alpha-V/beta-3 (ITGAV:ITGB3), activates FAK, MAPK and Akt signaling pathways and induces cell adhesion and cell migration. Secreted from podocytes, may modulate properties of glomerular endothelial cells involving integrin alpha-V/beta-3 and Akt signaling. May increase the motility of podocytes. May induce actin filament rearrangements in podocytes implicating integrin alpha-V/beta-3 and Rac1 activation. Binds to hematopoietic stem cells (HSC) and is involved in the regulation of HSC activity probably implicating down-regulation of IKZF1/IKAROS (By similarity).

References:

[1]. Anna Tikka, et al. Silencing of ANGPTL 3 (angiopoietin-like protein 3) in human hepatocytes results in decreased expression of gluconeogenic genes and reduced triacylglycerol-rich VLDL secretion upon insulin stimulation. Biosci Rep. 2014 Dec 12;34(6):e00160. [Content Brief]

[2]. Yunling Li, et al. Angiopoietin-like protein 3 modulates barrier properties of human glomerular endothelial cells through a possible signaling pathway involving phosphatidylinositol-3 kinase/protein kinase B and integrin alphaVbeta3. Acta Biochim Biophys Sin (Shanghai). 2008 Jun;40(6):459-65. [Content Brief]

[3]. Ryuta Koishi, et al. Angptl3 regulates lipid metabolism in mice. Nat Genet. 2002 Feb;30(2):151-7. [Content Brief]

[4]. Mitsuru Shimamura, et al. Angiopoietin-like protein 3, a hepatic secretory factor, activates lipolysis in adipocytes. Biochem Biophys Res Commun. 2003 Feb 7;301(2):604-9. [Content Brief]

[5]. Lu Shan, et al. The angiopoietin-like proteins ANGPTL3 and ANGPTL4 inhibit lipoprotein lipase activity through distinct mechanisms. J Biol Chem. 2009 Jan 16;284(3):1419-24. [Content Brief]

[6]. Tetsuya Shimizugawa, et al. ANGPTL3 decreases very low density lipoprotein triglyceride clearance by inhibition of lipoprotein lipase. J Biol Chem. 2002 Sep 13;277(37):33742-8. [Content Brief]

[7]. William K Sonnenburg, et al. GPIHBP1 stabilizes lipoprotein lipase and prevents its inhibition by angiopoietin-like 3 and angiopoietin-like 4. J Lipid Res. 2009 Dec;50(12):2421-9. [Content Brief]

[8]. Jun Liu, et al. Angiopoietin-like protein 3 inhibits lipoprotein lipase activity through enhancing its cleavage by proprotein convertases. J Biol Chem. 2010 Sep 3;285(36):27561-70. [Content Brief]

[9]. Mitsuru Shimamura, et al. Angiopoietin-like protein3 regulates plasma HDL cholesterol through suppression of endothelial lipase. Arterioscler Thromb Vasc Biol. 2007 Feb;27(2):366-72. [Content Brief]

[10]. Gieri Camenisch, et al. ANGPTL3 stimulates endothelial cell adhesion and migration via integrin alpha vbeta 3 and induces blood vessel formation in vivo. J Biol Chem. 2002 May 10;277(19):17281-90. [Content Brief]

[11]. Mitsuru Ono, et al. Protein region important for regulation of lipid metabolism in angiopoietin-like 3 (ANGPTL3): ANGPTL3 is cleaved and activated in vivo. J Biol Chem. 2003 Oct 24;278(43):41804-9. [Content Brief]

[12]. Marius R Robciuc, et al. Angptl3 deficiency is associated with increased insulin sensitivity, lipoprotein lipase activity, and decreased serum free fatty acids. Arterioscler Thromb Vasc Biol. 2013 Jul;33(7):1706-13. [Content Brief]

[13]. E-Chiang Lee, et al. Identification of a new functional domain in angiopoietin-like 3 (ANGPTL3) and angiopoietin-like 4 (ANGPTL4) involved in binding and inhibition of lipoprotein lipase (LPL). J Biol Chem. 2009 May 15;284(20):13735-13745. [Content Brief]

Biomedical Dictionary

The Biomedical Dictionary is a comprehensive and professional collection of biological academic terms and subject datas. All explanations are supported by authoritative books or high impact factor literatures, and you can acquire accurate explanations of the biomedical terms you want to know.

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z #

Name
Email *

	Sorry, but the email address you supplied was invalid.