The very low density lipoprotein receptor

Yamamoto, Tokuo; Takahashi, Sadao; Sakai, Juro; Kawarabayasi, Yutaka

doi:10.1016/1050-1738(93)90015-x

Cited by 47 publications

(24 citation statements)

References 23 publications

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“…Plasmids encoding the human VLDL receptor (ph-VLR2) or pSV2-neo, which contains the neomycin resistance gene, were transfected to ldlA-7 cells (mutant Chinese hamster ovary cells that lack LDL receptors) which was kindly provided by Dr. Monty Krieger (Department of Biology, Massachusetts Institute of Technology, Cambridge, MA) using lipofectin as described previously [1][2][3]9,12]. Positive cell clones for the human VLDL receptor were designated VLDL-R cells.…”

Section: Isolation Of Transfected Cellsmentioning

confidence: 99%

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Very low density lipoprotein receptor binds apolipoprotein E2/2 as well as apolipoprotein E3/3

et al. 1996

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Section: Isolation Of Transfected Cellsmentioning

confidence: 99%

“…The VLDL receptor has eight repeats whereas the LDL receptor has seven. The VLDL receptor binds with high affinity to particles containing apolipoprotein E (apoE), but not LDL [1,2]. The human VLDL receptor has been isolated from monocytic leukemia cells (THP-1) and characterized; its expression is not downregulated by sterols [3].…”

Section: Introductionmentioning

confidence: 99%

Very low density lipoprotein receptor binds apolipoprotein E2/2 as well as apolipoprotein E3/3

et al. 1996

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“…Yamamoto et al [153] were the first to clone and characterize VLDL receptor cDNAs from rabbit heart and human macrophage cells [154]. VLDL receptor mRNA are highly abundant in heart, muscle, adipose tissue and brain and are barely detectable in the liver where LDL receptors are expressed abundantly, suggesting that this receptor may be responsible for the entry of triglyceride rich lipoproteins into muscle and fat.…”

Section: Ldl Receptor and Apolipoproteinsmentioning

confidence: 99%

Recent advances in physiological lipoprotein metabolism

Ramasamy

2014

Clinical Chemistry and Laboratory Medicine (CCLM)

182

159

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Abstract:Research into lipoprotein metabolism has developed because understanding lipoprotein metabolism has important clinical indications. Lipoproteins are risk factors for cardiovascular disease. Recent advances include the identification of factors in the synthesis and secretion of triglyceride rich lipoproteins, chylomicrons (CM) and very low density lipoproteins (VLDL). These included the identification of microsomal transfer protein, the cotranslational targeting of apoproteinB (apoB) for degradation regulated by the availability of lipids, and the characterization of transport vesicles transporting primordial apoB containing particles to the Golgi. The lipase maturation factor 1, glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 and an angiopoietin-like protein play a role in lipoprotein lipase (LPL)-mediated hydrolysis of secreted CMs and VLDL so that the right amount of fatty acid is delivered to the right tissue at the right time. Expression of the low density lipoprotein (LDL) receptor is regulated at both transcriptional and posttranscriptional level. Proprotein convertase subtilisin/ kexin type 9 (PCSK9) has a pivotal role in the degradation of LDL receptor. Plasma remnant lipoproteins bind to specific receptors in the liver, the LDL receptor, VLDL receptor and LDL receptor-like proteins prior to removal from the plasma. Reverse cholesterol transport occurs when lipid free apoAI recruits cholesterol and phospholipid to assemble high density lipoprotein (HDL) particles. The discovery of ABC transporters (ABCA1 and ABCG1) and scavenger receptor class B type I (SR-BI) provided further information on the biogenesis of HDL. In humans HDLcholesterol can be returned to the liver either by direct uptake by SR-BI or through cholesteryl ester transfer protein exchange of cholesteryl ester for triglycerides in apoB lipoproteins, followed by hepatic uptake of apoB containing particles. Cholesterol content in cells is regulated by several transcription factors, including the liver X receptor and sterol regulatory element binding protein. This review summarizes recent advances in knowledge of the molecular mechanisms regulating lipoprotein metabolism.Keywords: ABCA1; angiopoietin-like proteins; apoC; apoAI; apolipoprotein E (apoE); cholesterol ester transfer protein; chylomicron; LDL receptor; lecithin cholesterol acyl transferase; lipoprotein(a); lipoprotein lipase; microsomal transfer protein; propertin convertase subtilisin/ kexin type 9; SR-BI; phospholipid transfer protein; very low density lipoproteins (VLDL). Abstract 1695

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“…Although the LDL-R is highly expressed in liver and promotes LDL uptake and clearance (21), the VLDL-R is most abundant in heart and skeletal muscle (22), suggesting involvement in the uptake of triglyceride-rich lipoproteins in tissues dependent on fatty acid metabolism (2,7,8). However, the broad ligand specificity of the VLDL-R as well as the lack of coordinate regulation between the VLDL-R and lipoprotein lipase suggests that this receptor may also function in other processes distinct from lipid metabolism (23).…”

Section: The Very Low Density Lipoprotein Receptor (Vldl-r)mentioning

confidence: 99%

“…Despite this homology, however, the ligand binding specificity of these receptors differs. Though both receptors bind apoE-containing lipoproteins (6,7,9,10), only the LDL receptor binds lipoproteins containing apoB-100 (6, 7), whereas the VLDL-R binds several additional ligands such as lipoprotein lipase (9), (11) urokinase-type plasminogen activator:plasminogen activator inhibitor type 1 (u-PA:PAI-1) complexes (11,12), and Lp(a) (13). Finally, the 39-kDa receptor-associated protein (RAP), which co-purifies with (14,15) and binds with high affinity to the LDL receptor-related protein/␣ 2 -macroglobulin receptor (16 -18), binds tightly to the VLDL-R (19) but with only low affinity to the LDL-R (19,20).…”

mentioning

confidence: 99%

Regulation of the Ligand Binding Activity of the Human Very Low Density Lipoprotein Receptor by Protein Kinase C-dependent Phosphorylation

Sakthivel¹,

Zhang²,

Strickland³

et al. 2001

Journal of Biological Chemistry

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The very low density lipoprotein receptor (VLDL-R) binds and internalizes several ligands, including very low density lipoprotein (VLDL), urokinase-type plasminogen activator:plasminogen activator inhibitor type 1 complexes, lipoprotein lipase, and the 39-kDa receptor-associated protein that copurifies with the low density lipoprotein receptor-related protein/␣ 2 -macroglobulin receptor. Although several agonists regulate VLDL-R mRNA and/or protein expression, post-transcriptional regulation of receptor activity has not been described. Here, we report that the ligand binding activity of the VLDL-R in THP-1 monocytic cells, endothelial cells, smooth muscle cells, and VLDL-R-transfected HEK 293 cells is diminished after treatment with phorbol 12-myristate 13-acetate. This response was blocked by inhibitors of protein kinase C (PK-C), including a specific inhibitor of the PK-C ␤II isoform, and was associated with phosphorylation of serine residues in the cytoplasmic domain of the receptor. Culture of endothelial cells in the presence of high glucose concentrations, which stimulate diacylglycerol synthesis and PK-C ␤II activation, also induced a PK-C-dependent loss of VLDL-R ligand binding activity. Taken together, these studies demonstrate that the ligand binding activity of the VLDL-R is regulated by PK-C-dependent phosphorylation and that hyperglycemia may diminish VLDL-R activity. The very low density lipoprotein receptor (VLDL-R)1 is a member of the low density lipoprotein receptor (LDL-R) family, which encompasses several structurally related proteins such as the LDL receptor-related protein/␣ 2 -macroglobulin receptor, gp330 (megalin), and apoE receptor 2 (1-4) among others. Members of this family are characterized by a cytoplasmic domain NPXY sequence that mediates ligand internalization through clathrin-coated pits (5) and an extracellular domain comprised of cysteine-rich complement-type and epidermal growth factor precursor-like repeats that regulate ligand binding specificity (2). Except for the presence of an additional complement-type repeat in its extracellular domain, the domain structure of the VLDL-R is identical to that of the LDL-R (6 -8). Despite this homology, however, the ligand binding specificity of these receptors differs. Though both receptors bind apoE-containing lipoproteins (6, 7, 9, 10), only the LDL receptor binds lipoproteins containing apoB-100 (6, 7), whereas the VLDL-R binds several additional ligands such as lipoprotein lipase (9), (11) urokinase-type plasminogen activator:plasminogen activator inhibitor type 1 (u-PA:PAI-1) complexes (11,12), and Lp(a) (13). Finally, the 39-kDa receptor-associated protein (RAP), which co-purifies with (14, 15) and binds with high affinity to the LDL receptor-related protein/␣ 2 -macroglobulin receptor (16 -18), binds tightly to the VLDL-R (19) but with only low affinity to the 20).Differences in the tissue distribution of the LDL and VLDL receptors also suggest non-overlapping physiologic functions. Although the LDL-R is highly expressed in liver...

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The very low density lipoprotein receptor

Cited by 47 publications

References 23 publications

Very low density lipoprotein receptor binds apolipoprotein E2/2 as well as apolipoprotein E3/3

Very low density lipoprotein receptor binds apolipoprotein E2/2 as well as apolipoprotein E3/3

Recent advances in physiological lipoprotein metabolism

Regulation of the Ligand Binding Activity of the Human Very Low Density Lipoprotein Receptor by Protein Kinase C-dependent Phosphorylation

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