同: α-Macroglobulin receptor, Low- density lipoprotein receptor- related protein

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/11/23 22:31:38」(JST)

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Low density lipoprotein receptor-related protein 1 (LRP1), also known as alpha-2-macroglobulin receptor (A2MR), apolipoprotein E receptor (APOER) or cluster of differentiation 91 (CD91), is a protein forming a receptor found in the plasma membrane of cells involved in receptor-mediated endocytosis. In humans, the LRP1 protein is encoded by the LRP1 gene.^[4]^[5]^[6] LRP1 is also a key signalling protein and, thus, involved in various biological processes, such as lipoprotein metabolism and cell motility, and diseases, such as neurodegenerative diseases, atherosclerosis, and cancer.^[7]^[8]

Structure

The LRP1 gene encodes a 600 kDa precursor protein that is processed by furin in the trans-Golgi complex, resulting in a 515 kDa alpha-chain and an 85 kDa beta-chain associated noncovalently.^[7]^[9]^[10] As a member of the LDLR family, LRP1 contains cysteine-rich complement-type repeats, EGF (gene) repeats, β-propeller domains, a transmembrane domain, and a cytoplasmic domain.^[8] The cytoplasmic domain of LRP1 is the alpha-chain, which comprises four ligand-binding domains (numbered I-IV) containing two, eight, ten, and eleven cysteine-rich complement-type repeats, respectively.^[7]^[8]^[9]^[10] These repeats bind extracellular matrix proteins, growth factors, proteases, protease inhibitor complexes, and other proteins involved in lipoprotein metabolism.^[7]^[8] Of the four domains, II and IV bind the majority of the protein’s ligands.^[10] The EGF repeats and β-propeller domains serve to release ligands in low pH conditions, such as inside endosomes, with the β-propeller postulated to displace the ligand at the ligand binding repeats.^[8] The transmembrane domain is the β-chain, which contains a 100-residue cytoplasmic tail. This tail contains two NPxY motifs that are responsible for the protein’s function in endocytosis and signal transduction.^[7]

Function

LRP1 is a member of the LDLR family and ubiquitously expressed in multiple tissues, though it is most abundant in vascular smooth muscle cells (SMCs), hepatocytes, and neurons.^[7]^[8] LRP1 plays a key role in intracellular signaling and endocytosis, which thus implicate it in many cellular and biological processes, including lipid and lipoprotein metabolism, protease degradation, platelet derived growth factor receptor regulation, integrin maturation and recycling, regulation of vascular tone, regulation of blood brain barrier permeability, cell growth, cell migration, inflammation, and apoptosis, as well as diseases such as neurodegenerative diseases, atherosclerosis, and cancer.^[6]^[7]^[8]^[9]^[10] To elaborate, LRP1 mainly contributes to regulation of protein activity by binding target proteins as a co-receptor, in conjunction with integral membrane proteins or adaptor proteins like uPA, to the lysosome for degradation.^[8]^[9]^[10] In lipoprotein metabolism, the interaction between LRP1 and APOE stimulates a signaling pathway that leads to elevated intracellular cAMP levels, increased protein kinase A activity, inhibited SMC migration, and ultimately, protection against vascular disease.^[8] While membrane-bound LRP1 performs endocytic clearance of proteases and inhibitors, proteolytic cleavage of its ectodomain allows the free LRP1 to compete with the membrane-bound form and prevent their clearance.^[7] Moreover, it is continuously endocytosed from the membrane and recycled back to the cell surface.^[8] Though the role of LRP1 in apoptosis is unclear, it is required for tPA to bind LRP1 in order to trigger the ERK1/2 signal cascade and promote cell survival.^[11]

Clinical significance

Alzheimer's disease

Neurons require cholesterol to function. Cholesterol is imported into the neuron by apolipoprotein E (apoE) via LRP1 receptors on the cell surface. It is thought that a causal factor in Alzheimer's is the malfunction of this process which damages neurons by starving them of cholesterol.^[12]

Over-accumulation of copper in the brain is associated with reduced LRP1 mediated clearance of amyloid beta across the blood brain barrier. This defective clearance may contribute to the buildup of neurotoxic amyloid-beta that is thought to contribute to Alzheimer's disease.^[13]

Cardiovascular disease

Studies have elucidated different roles for LRP1 in cellular processes relevant for cardiovascular disease. Atherosclerosis is the primary cause of cardiovascular disease such as stroke and heart attacks. In the liver LRP1 is important for the removal of atherogenic lipoproteins (Chylomicron remnants, VLDL) and other proatherogenic ligands from the circulation.^[14]^[15] LRP1 has a cholesterol-independent role in atherosclerosis by modulating the activity and cellular localization of the PDGFR-β in vascular smooth muscle cells.^[16]^[17] Finally, LRP1 in macrophages has an effect on atherosclerosis through the modulation of the extracellular matrix and inflammatory responses.^[18]^[19]

Cancer

LRP1 is involved in tumorigenesis, and is proposed to be a tumor suppressor. Notably, LRP1 functions in clearing proteases such as plasmin, urokinase-type plasminogen activator, and metalloproteinases, which contributes to prevention of cancer invasion, while its absence is linked to increased cancer invasion. However, the exact mechanisms require further study, as other studies have shown that LRP1 may also promote cancer invasion. One possible mechanism for the inhibitory function of LRP1 in cancer involves the LRP1-dependent endocytosis of 2′-hydroxycinnamaldehyde (HCA), resulting in decreased pepsin levels and, consequently, tumor progression.^[8] Alternatively, LRP1 may regulate focal adhesion disassembly of cancer cells through the ERK and JNK pathways to aid invasion.^[7] Moreover, LRP1 interacts with PAI-1 to recruit mast cells (MCs) and induce their degranulation, resulting in the release of MC mediators, activation of an inflammatory response, and development of glioma.^[9]

Interactions

LRP1 has been shown to interact with:

A2-Macroglobulin,^[8]
β-amyloid precursor protein,^[8]
APBB1,^[20]
APOE,^[8]^[21]^[22]
Aprotinin,^[8]
C1S/C1q inhibitor,^[8]
CALR,^[8]^[23]
CD44,^[7]
Chylomicron,^[8]
Circumsporozoite protein,^[8]
Collectin,^[8]
Complement C3,^[8]
CTGF,^[8]
DLG4,^[24]
Elastase,^[8]
Factor IXa,^[8]
Factor VIIa,^[8]
Fibronectin,^[8]
Gentamicin,^[8]
GIPC1,^[24]
heparin cofactor II,^[8]
Hepatic lipase,^[8]
ITGB1BP1,^[24]
Lactoferrin,^[8]
Lipoprotein lipase,^[8]
LPL,^[25]^[26]^[27]
MAPK8IP1,^[24]
MAPK8IP2,^[24]
Midkine,^[8]
MMP13,^[7]^[8]
MMP2,^[7]
MMP9,^[7]^[8]
Neuroserpin,^[8]
Nexin-1,^[8]
NOS1AP,^[24]
PAI 2,^[7]
PAI-1,^[7]^[9]
PDGF,^[8]
tPA,^[7]^[8]
uPA,^[7]^[8]
Polymyxin B,^[8]
Protein C inhibitor,^[8]
Pseudomonas exotoxin A,^[8]
RAP,^[8]
Ricin A,^[8]
SHC1,^[28]^[29] and
Sphingolipid activator protein,^[8]
SYNJ2BP.^[24]
Tat,^[8]
Thrombin,^[8]
THBS1,^[8]^[30]^[31]^[32]
Thrombospondin 2,^[8]
TIMP1,^[7]
TIMP2,^[7]
TIMP3,^[7]
Tissue factor pathway inhibitor,^[8]
PLAT,^[33]^[34]
Transforming growth factor-β,^[8]
PLAUR,^[35]
VLDL,^[8]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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|px|alt=Statin Pathway edit]]

File:StatinPathway_WP430.png

Statin Pathway edit

^ The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".

References

^ "Diseases that are genetically associated with LRP1 view/edit references on wikidata".
^ "Human PubMed Reference:".
^ "Mouse PubMed Reference:".
^ Herz J, Hamann U, Rogne S, Myklebost O, Gausepohl H, Stanley KK (Dec 1988). "Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor". The EMBO Journal. 7 (13): 4119–27. PMC 455121. PMID 3266596.
^ Myklebost O, Arheden K, Rogne S, Geurts van Kessel A, Mandahl N, Herz J, Stanley K, Heim S, Mitelman F (Jul 1989). "The gene for the human putative apoE receptor is on chromosome 12 in the segment q13-14". Genomics. 5 (1): 65–9. doi:10.1016/0888-7543(89)90087-6. PMID 2548950.
^ ^a ^b "Entrez Gene: LRP1 low density lipoprotein receptor-related protein 1".
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t Etique N, Verzeaux L, Dedieu S, Emonard H (2013). "LRP-1: a checkpoint for the extracellular matrix proteolysis". BioMed Research International. 2013: 152163. doi:10.1155/2013/152163. PMID 23936774.
^ ^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 ^aa ^ab ^ac ^ad ^ae ^af ^ag ^ah ^ai ^aj ^ak ^al ^am ^an ^ao ^ap ^aq ^ar ^as ^at ^au ^av ^aw ^ax ^ay ^az Lillis AP, Mikhailenko I, Strickland DK (Aug 2005). "Beyond endocytosis: LRP function in cell migration, proliferation and vascular permeability". Journal of Thrombosis and Haemostasis. 3 (8): 1884–93. doi:10.1111/j.1538-7836.2005.01371.x. PMID 16102056.
^ ^a ^b ^c ^d ^e ^f Roy A, Coum A, Marinescu VD, Põlajeva J, Smits A, Nelander S, Uhrbom L, Westermark B, Forsberg-Nilsson K, Pontén F, Tchougounova E (Jun 2015). "Glioma-derived plasminogen activator inhibitor-1 (PAI-1) regulates the recruitment of LRP1 positive mast cells". Oncotarget. 6: 23647–61. doi:10.18632/oncotarget.4640. PMID 26164207.
^ ^a ^b ^c ^d ^e Kang HS, Kim J, Lee HJ, Kwon BM, Lee DK, Hong SH (Aug 2014). "LRP1-dependent pepsin clearance induced by 2'-hydroxycinnamaldehyde attenuates breast cancer cell invasion". The International Journal of Biochemistry & Cell Biology. 53: 15–23. doi:10.1016/j.biocel.2014.04.021. PMID 24796846.
^ Hu K, Lin L, Tan X, Yang J, Bu G, Mars WM, Liu Y (Mar 2008). "tPA protects renal interstitial fibroblasts and myofibroblasts from apoptosis". Journal of the American Society of Nephrology. 19 (3): 503–14. doi:10.1681/ASN.2007030300. PMID 18199803.
^ Liu Q, Zerbinatti CV, Zhang J, Hoe HS, Wang B, Cole SL, Herz J, Muglia L, Bu G (Oct 2007). "Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1". Neuron. 56 (1): 66–78. doi:10.1016/j.neuron.2007.08.008. PMC 2045076. PMID 17920016.
^ Singh I, Sagare AP, Coma M, Perlmutter D, Gelein R, Bell RD, Deane RJ, Zhong E, Parisi M, Ciszewski J, Kasper RT, Deane R (Sep 2013). "Low levels of copper disrupt brain amyloid-β homeostasis by altering its production and clearance". Proceedings of the National Academy of Sciences of the United States of America. 110 (36): 14771–6. doi:10.1073/pnas.1302212110. PMC 3767519. PMID 23959870.
^ Gordts PL, Reekmans S, Lauwers A, Van Dongen A, Verbeek L, Roebroek AJ (Sep 2009). "Inactivation of the LRP1 intracellular NPxYxxL motif in LDLR-deficient mice enhances postprandial dyslipidemia and atherosclerosis". Arteriosclerosis, Thrombosis, and Vascular Biology. 29 (9): 1258–64. doi:10.1161/ATVBAHA.109.192211. PMID 19667105.
^ Rohlmann A, Gotthardt M, Hammer RE, Herz J (Feb 1998). "Inducible inactivation of hepatic LRP gene by cre-mediated recombination confirms role of LRP in clearance of chylomicron remnants". The Journal of Clinical Investigation. 101 (3): 689–95. doi:10.1172/JCI1240. PMC 508614. PMID 9449704.
^ Boucher P, Gotthardt M, Li WP, Anderson RG, Herz J (Apr 2003). "LRP: role in vascular wall integrity and protection from atherosclerosis". Science. 300 (5617): 329–32. doi:10.1126/science.1082095. PMID 12690199.
^ Boucher P, Li WP, Matz RL, Takayama Y, Auwerx J, Anderson RG, Herz J (2007). "LRP1 functions as an atheroprotective integrator of TGFbeta and PDFG signals in the vascular wall: implications for Marfan syndrome". PLOS ONE. 2 (5): e448. doi:10.1371/journal.pone.0000448. PMC 1864997. PMID 17505534.
^ Yancey PG, Ding Y, Fan D, Blakemore JL, Zhang Y, Ding L, Zhang J, Linton MF, Fazio S (Jul 2011). "Low-density lipoprotein receptor-related protein 1 prevents early atherosclerosis by limiting lesional apoptosis and inflammatory Ly-6Chigh monocytosis: evidence that the effects are not apolipoprotein E dependent". Circulation. 124 (4): 454–64. doi:10.1161/CIRCULATIONAHA.111.032268. PMC 3144781. PMID 21730304.
^ Overton CD, Yancey PG, Major AS, Linton MF, Fazio S (Mar 2007). "Deletion of macrophage LDL receptor-related protein increases atherogenesis in the mouse". Circulation Research. 100 (5): 670–7. doi:10.1161/01.RES.0000260204.40510.aa. PMID 17303763.
^ Trommsdorff M, Borg JP, Margolis B, Herz J (Dec 1998). "Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein". The Journal of Biological Chemistry. 273 (50): 33556–60. doi:10.1074/jbc.273.50.33556. PMID 9837937.
^ Poswa M (Mar 1977). "[Team growth by acquiring an apprentice]". Quintessenz Journal. 7 (3): 21–3. PMID 277965.
^ Kowal RC, Herz J, Goldstein JL, Esser V, Brown MS (Aug 1989). "Low density lipoprotein receptor-related protein mediates uptake of cholesteryl esters derived from apoprotein E-enriched lipoproteins". Proceedings of the National Academy of Sciences of the United States of America. 86 (15): 5810–4. Bibcode:1989PNAS...86.5810K. doi:10.1073/pnas.86.15.5810. PMC 297720. PMID 2762297.
^ Orr AW, Pedraza CE, Pallero MA, Elzie CA, Goicoechea S, Strickland DK, Murphy-Ullrich JE (Jun 2003). "Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly". The Journal of Cell Biology. 161 (6): 1179–89. doi:10.1083/jcb.200302069. PMC 2172996. PMID 12821648.
^ ^a ^b ^c ^d ^e ^f ^g Gotthardt M, Trommsdorff M, Nevitt MF, Shelton J, Richardson JA, Stockinger W, Nimpf J, Herz J (Aug 2000). "Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction". The Journal of Biological Chemistry. 275 (33): 25616–24. doi:10.1074/jbc.M000955200. PMID 10827173.
^ Williams SE, Inoue I, Tran H, Fry GL, Pladet MW, Iverius PH, Lalouel JM, Chappell DA, Strickland DK (Mar 1994). "The carboxyl-terminal domain of lipoprotein lipase binds to the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP) and mediates binding of normal very low density lipoproteins to LRP". The Journal of Biological Chemistry. 269 (12): 8653–8. PMID 7510694.
^ Nykjaer A, Nielsen M, Lookene A, Meyer N, Røigaard H, Etzerodt M, Beisiegel U, Olivecrona G, Gliemann J (Dec 1994). "A carboxyl-terminal fragment of lipoprotein lipase binds to the low density lipoprotein receptor-related protein and inhibits lipase-mediated uptake of lipoprotein in cells". The Journal of Biological Chemistry. 269 (50): 31747–55. PMID 7989348.
^ Chappell DA, Fry GL, Waknitz MA, Iverius PH, Williams SE, Strickland DK (Dec 1992). "The low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor binds and mediates catabolism of bovine milk lipoprotein lipase". The Journal of Biological Chemistry. 267 (36): 25764–7. PMID 1281473.
^ Barnes H, Ackermann EJ, van der Geer P (Jun 2003). "v-Src induces Shc binding to tyrosine 63 in the cytoplasmic domain of the LDL receptor-related protein 1". Oncogene. 22 (23): 3589–97. doi:10.1038/sj.onc.1206504. PMID 12789267.
^ Loukinova E, Ranganathan S, Kuznetsov S, Gorlatova N, Migliorini MM, Loukinov D, Ulery PG, Mikhailenko I, Lawrence DA, Strickland DK (May 2002). "Platelet-derived growth factor (PDGF)-induced tyrosine phosphorylation of the low density lipoprotein receptor-related protein (LRP). Evidence for integrated co-receptor function between LRP and the PDGF". The Journal of Biological Chemistry. 277 (18): 15499–506. doi:10.1074/jbc.M200427200. PMID 11854294.
^ Wang S, Herndon ME, Ranganathan S, Godyna S, Lawler J, Argraves WS, Liau G (Mar 2004). "Internalization but not binding of thrombospondin-1 to low density lipoprotein receptor-related protein-1 requires heparan sulfate proteoglycans". Journal of Cellular Biochemistry. 91 (4): 766–76. doi:10.1002/jcb.10781. PMID 14991768.
^ Mikhailenko I, Krylov D, Argraves KM, Roberts DD, Liau G, Strickland DK (Mar 1997). "Cellular internalization and degradation of thrombospondin-1 is mediated by the amino-terminal heparin binding domain (HBD). High affinity interaction of dimeric HBD with the low density lipoprotein receptor-related protein". The Journal of Biological Chemistry. 272 (10): 6784–91. doi:10.1074/jbc.272.10.6784. PMID 9045712.
^ Godyna S, Liau G, Popa I, Stefansson S, Argraves WS (Jun 1995). "Identification of the low density lipoprotein receptor-related protein (LRP) as an endocytic receptor for thrombospondin-1". The Journal of Cell Biology. 129 (5): 1403–10. doi:10.1083/jcb.129.5.1403. PMC 2120467. PMID 7775583.
^ Zhuo M, Holtzman DM, Li Y, Osaka H, DeMaro J, Jacquin M, Bu G (Jan 2000). "Role of tissue plasminogen activator receptor LRP in hippocampal long-term potentiation". The Journal of Neuroscience. 20 (2): 542–9. PMID 10632583.
^ Orth K, Madison EL, Gething MJ, Sambrook JF, Herz J (Aug 1992). "Complexes of tissue-type plasminogen activator and its serpin inhibitor plasminogen-activator inhibitor type 1 are internalized by means of the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor". Proceedings of the National Academy of Sciences of the United States of America. 89 (16): 7422–6. doi:10.1073/pnas.89.16.7422. PMC 49722. PMID 1502153.
^ Czekay RP, Kuemmel TA, Orlando RA, Farquhar MG (May 2001). "Direct binding of occupied urokinase receptor (uPAR) to LDL receptor-related protein is required for endocytosis of uPAR and regulation of cell surface urokinase activity". Molecular Biology of the Cell. 12 (5): 1467–79. doi:10.1091/mbc.12.5.1467. PMC 34598. PMID 11359936.

External links

CD91 Antigen at the US National Library of Medicine Medical Subject Headings (MeSH)

English Journal

Regulatory B Cells Are Functionally Impaired in Patients Having Hemophilia A With Inhibitors.

Boulassel MR1,2, Al-Ghonimi M1, Al-Balushi B2, Al-Naamani A1, Al-Qarni Z1, Wali Y3,4, Elshinawy M3,4, Al-Shezawi M3, Khan H2, Nazir H3,4, Khater D3,4, Pathare A2, Al-Kindi S2.
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.Clin Appl Thromb Hemost.2018 May;24(4):618-624. doi: 10.1177/1076029617702244. Epub 2017 Apr 10.
PMID 28393618

SjCRT, a recombinant Schistosoma japonicum calreticulin, induces maturation of dendritic cells and a Th1-polarized immune response in mice.

Ma L1, Li D1,2, Yuan C1,3, Zhang X1, Ta N1, Zhao X1, Li Y1,2, Feng X4.
Parasites & vectors.Parasit Vectors.2017 Nov 13;10(1):570. doi: 10.1186/s13071-017-2516-7.
PMID 29132406

Extracellular Hsp70 Enhances Mesoangioblast Migration via an Autocrine Signaling Pathway.

Barreca MM1, Spinello W1, Cavalieri V1, Turturici G1, Sconzo G1, Kaur P2, Tinnirello R3, Asea AA4, Geraci F1,5.
Journal of cellular physiology.J Cell Physiol.2017 Jul;232(7):1845-1861. doi: 10.1002/jcp.25722. Epub 2017 Jan 31.
PMID 27925208

Japanese Journal

体内・細胞内動態制御機能を搭載した熱ショックタンパク質の開発とワクチンデリバリーへの応用(誌上シンポジウム)

藥學雜誌 127(2), 293-300, 2007-02-01
NAID 110006163784

Essential role of CD91 in re-presentation of gp96-chaperoned peptides

Proc Natl Acad Sci USA 101, 6128-6133, 2004
NAID 80016640866

Heat Shock Proteins: Chaperoning of Innate and Adaptive Immunities

日本ハイパーサーミア学会誌 19(3), 131-139, 2003
NAID 130003646633

Related Pictures

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★リンクテーブル★

リンク元	「表面抗原分類」
関連記事	「CD」

「表面抗原分類」

LRP1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1CR8, 1D2L, 1J8E, 2FYJ, 2FYL, 2KNX, 2KNY
Identifiers
Aliases	LRP1, A2MR, APOER, APR, CD91, IGFBP3R, LRP, LRP1A, TGFBR5, low density lipoprotein receptor-related protein 1, LDL receptor related protein 1
External IDs	MGI: 96828 HomoloGene: 1744 GeneCards: LRP1
Genetically Related Diseases
	migraine, migraine without aura, abdominal aortic aneurysm
Gene ontology
Molecular function	• calcium ion binding; • apolipoprotein binding; • lipoprotein particle receptor binding; • protein complex binding; • metal ion binding; • lipoprotein transporter activity; • protease binding; • protein binding; • poly(A) RNA binding; • receptor activity; • low-density lipoprotein receptor activity;
Cellular component	• cytoplasm; • integral component of membrane; • endocytic vesicle membrane; • endosome; • membrane; • focal adhesion; • receptor complex; • plasma membrane; • integral component of plasma membrane; • lysosomal membrane; • neuronal cell body; • dendrite; • nucleolus; • clathrin-coated pit; • clathrin-coated vesicle; • nucleus;
Biological process	• lipoprotein metabolic process; • negative regulation of neuron apoptotic process; • negative regulation of platelet-derived growth factor receptor-beta signaling pathway; • negative regulation of neuron projection development; • endocytosis; • regulation of actin cytoskeleton organization; • regulation of phospholipase A2 activity; • beta-amyloid clearance; • negative regulation of Wnt signaling pathway; • aging; • negative regulation of smooth muscle cell migration; • positive regulation of lipid transport; • receptor-mediated endocytosis; • aorta morphogenesis; • retinoid metabolic process; • regulation of cholesterol transport; • positive regulation of protein transport; • apoptotic cell clearance; • multicellular organism development; • protein kinase C-activating G-protein coupled receptor signaling pathway; • positive regulation of cholesterol efflux; • cerebral cortex development; • cell proliferation; • lipoprotein transport;
	Sources:Amigo / QuickGO
RNA expression pattern
	; ;
	More reference expression data
Orthologs
	4035
	16971
	ENSG00000123384
	ENSMUSG00000040249
	Q07954
	Q91ZX7
	NM_002332
	NM_008512
	NP_002323.2
	NP_032538.2
	Wikidata
View/Edit Human	View/Edit Mouse

　　[★]

英: cluster of differentiation, CD

細胞の表面抗原を認識する抗体を整理した分類

Bリンパ球 CD10,CD19,CD20

Tリンパ球 CD2,CD3,CD5,CD7

幹細胞 CD34

顆粒球 CD13,CD33

単球 CD14：LPSをリガンドとし、Toll-like receptorと共役して細胞内シグナルを伝達する分子。

巨核球 CD41(GpIIb),CD42(GpIb)

NK細胞：CD16(IgGのFc部に対する受容体)、CD56(NCAM-I)

CD1	CD21	CD41	CD61	CD81
CD2	CD22	CD42	CD62	CD82
CD3	CD23	CD43	CD63	CD83
CD4	CD24	CD44	CD64	CD84
CD5	CD25	CD45	CD65	CD85
CD6	CD26	CD46	CD66	CD86
CD7	CD27	CD47	CD67	CD87
CD8	CD28	CD48	CD68	CD88
CD9	CD29	CD49	CD69	CD89
CD10	CD30	CD50	CD70	CD90
CD11	CD31	CD51	CD71	CD91
CD12	CD32	CD52	CD72	CD92
CD13	CD33	CD53	CD73	CD93
CD14	CD34	CD54	CD74	CD94
CD15	CD35	CD55	CD75	CD95
CD16	CD36	CD56	CD76	CD96
CD17	CD37	CD57	CD77	CD97
CD18	CD38	CD58	CD78	CD98
CD19	CD39	CD59	CD79	CD99
CD20	CD40	CD60	CD80	CD100

「CD」

　　[★]

[WikiPathways-36] The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430".

[1] "Diseases that are genetically associated with LRP1 view/edit references on wikidata".

[2] "Human PubMed Reference:".

[3] "Mouse PubMed Reference:".

[pmid3266596-4] Herz J, Hamann U, Rogne S, Myklebost O, Gausepohl H, Stanley KK (Dec 1988). "Surface location and high affinity for calcium of a 500-kd liver membrane protein closely related to the LDL-receptor suggest a physiological role as lipoprotein receptor". The EMBO Journal. 7 (13): 4119–27. PMC 455121. PMID 3266596.

[pmid2548950-5] Myklebost O, Arheden K, Rogne S, Geurts van Kessel A, Mandahl N, Herz J, Stanley K, Heim S, Mitelman F (Jul 1989). "The gene for the human putative apoE receptor is on chromosome 12 in the segment q13-14". Genomics. 5 (1): 65–9. doi:10.1016/0888-7543(89)90087-6. PMID 2548950.

[entrez-6] "Entrez Gene: LRP1 low density lipoprotein receptor-related protein 1".

[pmid23936774-7] ^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m ⁿ ^o ^p ^q ^r ^s ^t Etique N, Verzeaux L, Dedieu S, Emonard H (2013). "LRP-1: a checkpoint for the extracellular matrix proteolysis". BioMed Research International. 2013: 152163. doi:10.1155/2013/152163. PMID 23936774.

[pmid16102056-8] ^ ^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 ^aa ^ab ^ac ^ad ^ae ^af ^ag ^ah ^ai ^aj ^ak ^al ^am ^an ^ao ^ap ^aq ^ar ^as ^at ^au ^av ^aw ^ax ^ay ^az Lillis AP, Mikhailenko I, Strickland DK (Aug 2005). "Beyond endocytosis: LRP function in cell migration, proliferation and vascular permeability". Journal of Thrombosis and Haemostasis. 3 (8): 1884–93. doi:10.1111/j.1538-7836.2005.01371.x. PMID 16102056.

[pmid26164207-9] ^ ^a ^b ^c ^d ^e ^f Roy A, Coum A, Marinescu VD, Põlajeva J, Smits A, Nelander S, Uhrbom L, Westermark B, Forsberg-Nilsson K, Pontén F, Tchougounova E (Jun 2015). "Glioma-derived plasminogen activator inhibitor-1 (PAI-1) regulates the recruitment of LRP1 positive mast cells". Oncotarget. 6: 23647–61. doi:10.18632/oncotarget.4640. PMID 26164207.

[pmid24796846-10] Kang HS, Kim J, Lee HJ, Kwon BM, Lee DK, Hong SH (Aug 2014). "LRP1-dependent pepsin clearance induced by 2'-hydroxycinnamaldehyde attenuates breast cancer cell invasion". The International Journal of Biochemistry & Cell Biology. 53: 15–23. doi:10.1016/j.biocel.2014.04.021. PMID 24796846.

[11] Hu K, Lin L, Tan X, Yang J, Bu G, Mars WM, Liu Y (Mar 2008). "tPA protects renal interstitial fibroblasts and myofibroblasts from apoptosis". Journal of the American Society of Nephrology. 19 (3): 503–14. doi:10.1681/ASN.2007030300. PMID 18199803.

[12] Liu Q, Zerbinatti CV, Zhang J, Hoe HS, Wang B, Cole SL, Herz J, Muglia L, Bu G (Oct 2007). "Amyloid precursor protein regulates brain apolipoprotein E and cholesterol metabolism through lipoprotein receptor LRP1". Neuron. 56 (1): 66–78. doi:10.1016/j.neuron.2007.08.008. PMC 2045076. PMID 17920016.

[pmid23959870-13] Singh I, Sagare AP, Coma M, Perlmutter D, Gelein R, Bell RD, Deane RJ, Zhong E, Parisi M, Ciszewski J, Kasper RT, Deane R (Sep 2013). "Low levels of copper disrupt brain amyloid-β homeostasis by altering its production and clearance". Proceedings of the National Academy of Sciences of the United States of America. 110 (36): 14771–6. doi:10.1073/pnas.1302212110. PMC 3767519. PMID 23959870.

[pmid19667105-14] Gordts PL, Reekmans S, Lauwers A, Van Dongen A, Verbeek L, Roebroek AJ (Sep 2009). "Inactivation of the LRP1 intracellular NPxYxxL motif in LDLR-deficient mice enhances postprandial dyslipidemia and atherosclerosis". Arteriosclerosis, Thrombosis, and Vascular Biology. 29 (9): 1258–64. doi:10.1161/ATVBAHA.109.192211. PMID 19667105.

[pmid9449704-15] Rohlmann A, Gotthardt M, Hammer RE, Herz J (Feb 1998). "Inducible inactivation of hepatic LRP gene by cre-mediated recombination confirms role of LRP in clearance of chylomicron remnants". The Journal of Clinical Investigation. 101 (3): 689–95. doi:10.1172/JCI1240. PMC 508614. PMID 9449704.

[pmid12690199-16] Boucher P, Gotthardt M, Li WP, Anderson RG, Herz J (Apr 2003). "LRP: role in vascular wall integrity and protection from atherosclerosis". Science. 300 (5617): 329–32. doi:10.1126/science.1082095. PMID 12690199.

[pmid17505534-17] Boucher P, Li WP, Matz RL, Takayama Y, Auwerx J, Anderson RG, Herz J (2007). "LRP1 functions as an atheroprotective integrator of TGFbeta and PDFG signals in the vascular wall: implications for Marfan syndrome". PLOS ONE. 2 (5): e448. doi:10.1371/journal.pone.0000448. PMC 1864997. PMID 17505534.

[pmid21730304-18] Yancey PG, Ding Y, Fan D, Blakemore JL, Zhang Y, Ding L, Zhang J, Linton MF, Fazio S (Jul 2011). "Low-density lipoprotein receptor-related protein 1 prevents early atherosclerosis by limiting lesional apoptosis and inflammatory Ly-6Chigh monocytosis: evidence that the effects are not apolipoprotein E dependent". Circulation. 124 (4): 454–64. doi:10.1161/CIRCULATIONAHA.111.032268. PMC 3144781. PMID 21730304.

[pmid17303763-19] Overton CD, Yancey PG, Major AS, Linton MF, Fazio S (Mar 2007). "Deletion of macrophage LDL receptor-related protein increases atherogenesis in the mouse". Circulation Research. 100 (5): 670–7. doi:10.1161/01.RES.0000260204.40510.aa. PMID 17303763.

[pmid9837937-20] Trommsdorff M, Borg JP, Margolis B, Herz J (Dec 1998). "Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein". The Journal of Biological Chemistry. 273 (50): 33556–60. doi:10.1074/jbc.273.50.33556. PMID 9837937.

[21] Poswa M (Mar 1977). "[Team growth by acquiring an apprentice]". Quintessenz Journal. 7 (3): 21–3. PMID 277965.

[22] Kowal RC, Herz J, Goldstein JL, Esser V, Brown MS (Aug 1989). "Low density lipoprotein receptor-related protein mediates uptake of cholesteryl esters derived from apoprotein E-enriched lipoproteins". Proceedings of the National Academy of Sciences of the United States of America. 86 (15): 5810–4. Bibcode:1989PNAS...86.5810K. doi:10.1073/pnas.86.15.5810. PMC 297720. PMID 2762297.

[pmid12821648-23] Orr AW, Pedraza CE, Pallero MA, Elzie CA, Goicoechea S, Strickland DK, Murphy-Ullrich JE (Jun 2003). "Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly". The Journal of Cell Biology. 161 (6): 1179–89. doi:10.1083/jcb.200302069. PMC 2172996. PMID 12821648.

[pmid10827173-24] ^ ^a ^b ^c ^d ^e ^f ^g Gotthardt M, Trommsdorff M, Nevitt MF, Shelton J, Richardson JA, Stockinger W, Nimpf J, Herz J (Aug 2000). "Interactions of the low density lipoprotein receptor gene family with cytosolic adaptor and scaffold proteins suggest diverse biological functions in cellular communication and signal transduction". The Journal of Biological Chemistry. 275 (33): 25616–24. doi:10.1074/jbc.M000955200. PMID 10827173.

[pmid7510694-25] Williams SE, Inoue I, Tran H, Fry GL, Pladet MW, Iverius PH, Lalouel JM, Chappell DA, Strickland DK (Mar 1994). "The carboxyl-terminal domain of lipoprotein lipase binds to the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor (LRP) and mediates binding of normal very low density lipoproteins to LRP". The Journal of Biological Chemistry. 269 (12): 8653–8. PMID 7510694.

[pmid7989348-26] Nykjaer A, Nielsen M, Lookene A, Meyer N, Røigaard H, Etzerodt M, Beisiegel U, Olivecrona G, Gliemann J (Dec 1994). "A carboxyl-terminal fragment of lipoprotein lipase binds to the low density lipoprotein receptor-related protein and inhibits lipase-mediated uptake of lipoprotein in cells". The Journal of Biological Chemistry. 269 (50): 31747–55. PMID 7989348.

[pmid1281473-27] Chappell DA, Fry GL, Waknitz MA, Iverius PH, Williams SE, Strickland DK (Dec 1992). "The low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor binds and mediates catabolism of bovine milk lipoprotein lipase". The Journal of Biological Chemistry. 267 (36): 25764–7. PMID 1281473.

[pmid12789267-28] Barnes H, Ackermann EJ, van der Geer P (Jun 2003). "v-Src induces Shc binding to tyrosine 63 in the cytoplasmic domain of the LDL receptor-related protein 1". Oncogene. 22 (23): 3589–97. doi:10.1038/sj.onc.1206504. PMID 12789267.

[pmid11854294-29] Loukinova E, Ranganathan S, Kuznetsov S, Gorlatova N, Migliorini MM, Loukinov D, Ulery PG, Mikhailenko I, Lawrence DA, Strickland DK (May 2002). "Platelet-derived growth factor (PDGF)-induced tyrosine phosphorylation of the low density lipoprotein receptor-related protein (LRP). Evidence for integrated co-receptor function between LRP and the PDGF". The Journal of Biological Chemistry. 277 (18): 15499–506. doi:10.1074/jbc.M200427200. PMID 11854294.

[pmid14991768-30] Wang S, Herndon ME, Ranganathan S, Godyna S, Lawler J, Argraves WS, Liau G (Mar 2004). "Internalization but not binding of thrombospondin-1 to low density lipoprotein receptor-related protein-1 requires heparan sulfate proteoglycans". Journal of Cellular Biochemistry. 91 (4): 766–76. doi:10.1002/jcb.10781. PMID 14991768.

[pmid9045712-31] Mikhailenko I, Krylov D, Argraves KM, Roberts DD, Liau G, Strickland DK (Mar 1997). "Cellular internalization and degradation of thrombospondin-1 is mediated by the amino-terminal heparin binding domain (HBD). High affinity interaction of dimeric HBD with the low density lipoprotein receptor-related protein". The Journal of Biological Chemistry. 272 (10): 6784–91. doi:10.1074/jbc.272.10.6784. PMID 9045712.

[pmid7775583-32] Godyna S, Liau G, Popa I, Stefansson S, Argraves WS (Jun 1995). "Identification of the low density lipoprotein receptor-related protein (LRP) as an endocytic receptor for thrombospondin-1". The Journal of Cell Biology. 129 (5): 1403–10. doi:10.1083/jcb.129.5.1403. PMC 2120467. PMID 7775583.

[pmid10632583-33] Zhuo M, Holtzman DM, Li Y, Osaka H, DeMaro J, Jacquin M, Bu G (Jan 2000). "Role of tissue plasminogen activator receptor LRP in hippocampal long-term potentiation". The Journal of Neuroscience. 20 (2): 542–9. PMID 10632583.

[pmid1502153-34] Orth K, Madison EL, Gething MJ, Sambrook JF, Herz J (Aug 1992). "Complexes of tissue-type plasminogen activator and its serpin inhibitor plasminogen-activator inhibitor type 1 are internalized by means of the low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor". Proceedings of the National Academy of Sciences of the United States of America. 89 (16): 7422–6. doi:10.1073/pnas.89.16.7422. PMC 49722. PMID 1502153.

[pmid11359936-35] Czekay RP, Kuemmel TA, Orlando RA, Farquhar MG (May 2001). "Direct binding of occupied urokinase receptor (uPAR) to LDL receptor-related protein is required for endocytosis of uPAR and regulation of cell surface urokinase activity". Molecular Biology of the Cell. 12 (5): 1467–79. doi:10.1091/mbc.12.5.1467. PMC 34598. PMID 11359936.

v t e Proteins: clusters of differentiation (see also list of human clusters of differentiation)

1-50	CD1 a-c 1A 1D 1E CD2 CD3 γ δ ε CD4 CD5 CD6 CD7 CD8 a CD9 CD10 CD11 a b c d CD13 CD14 CD15 CD16 A B CD18 CD19 CD20 CD21 CD22 CD23 CD24 CD25 CD26 CD27 CD28 CD29 CD30 CD31 CD32 A B CD33 CD34 CD35 CD36 CD37 CD38 CD39 CD40 CD41 CD42 a b c d CD43 CD44 CD45 CD46 CD47 CD48 CD49 a b c d e f CD50

51-100	CD51 CD52 CD53 CD54 CD55 CD56 CD57 CD58 CD59 CD61 CD62 E L P CD63 CD64 A B C CD66 a b c d e f CD68 CD69 CD70 CD71 CD72 CD73 CD74 CD78 CD79 a b CD80 CD81 CD82 CD83 CD84 CD85 a d e h j k CD86 CD87 CD88 CD89 CD90 CD91 - CD92 CD93 CD94 CD95 CD96 CD97 CD98 CD99 CD100

101-150	CD101 CD102 CD103 CD104 CD105 CD106 CD107 a b CD108 CD109 CD110 CD111 CD112 CD113 CD114 CD115 CD116 CD117 CD118 CD119 CD120 a b CD121 a b CD122 CD123 CD124 CD125 CD126 CD127 CD129 CD130 CD131 CD132 CD133 CD134 CD135 CD136 CD137 CD138 CD140b CD141 CD142 CD143 CD144 CD146 CD147 CD148 CD150

151-200	CD151 CD152 CD153 CD154 CD155 CD156 a b c CD157 CD158 (a d e i k) CD159 a c CD160 CD161 CD162 CD163 CD164 CD166 CD167 a b CD168 CD169 CD170 CD171 CD172 a b g CD174 CD177 CD178 CD179 a b CD180 CD181 CD182 CD183 CD184 CD185 CD186 CD191 CD192 CD193 CD194 CD195 CD196 CD197 CDw198 CDw199 CD200

201-250	CD201 CD202b CD204 CD205 CD206 CD207 CD208 CD209 CDw210 a b CD212 CD213a 1 2 CD217 CD218 (a b) CD220 CD221 CD222 CD223 CD224 CD225 CD226 CD227 CD228 CD229 CD230 CD233 CD234 CD235 a b CD236 CD238 CD239 CD240CE CD240D CD241 CD243 CD244 CD246 CD247 - CD248 CD249

251-300	CD252 CD253 CD254 CD256 CD257 CD258 CD261 CD262 CD263 CD264 CD265 CD266 CD267 CD268 CD269 CD271 CD272 CD273 CD274 CD275 CD276 CD278 CD279 CD280 CD281 CD282 CD283 CD284 CD286 CD288 CD289 CD290 CD292 CDw293 CD294 CD295 CD297 CD298 CD299

301-350	CD300A CD301 CD302 CD303 CD304 CD305 CD306 CD307 CD309 CD312 CD314 CD315 CD316 CD317 CD318 CD320 CD321 CD322 CD324 CD325 CD326 CD328 CD329 CD331 CD332 CD333 CD334 CD335 CD336 CD337 CD338 CD339 CD340 CD344 CD349 CD350

v t e Lipids: lipoprotein particle metabolism

Lipoprotein particle classes and subclasses	delivery of TGs: Chylomicron VLDL delivery of C and CE: IDL LDL lb LDL sd LDL Lp(a) HDL

Apolipoproteins	APOA 1 2 4 5 APOB APOC 1 2 3 4 APOD APOE APOH SAA SAA1

Extracellular enzymes	LCAT LIPC LPL

Lipid transfer proteins	CETP MTTP PLTP

Cell surface receptors	HDL: SCARB1 IDL: LRP LRP1 LRP1B LRP2 LRP3 LRP4 LRP5 LRP5L LRP6 LRP8 LRP10 LRP11 LRP12 LDL: LDLR LRPAP1

ATP-binding cassette transporter	ABCA1 ABCG5 ABCG8

匿名

検索

案内

案内

CD91