LRP1

Low density lipoprotein receptor-related protein 1
	; PDB rendering based on 1cr8.
Available structures
PDB	1CR8, 1D2L, 1J8E, 2FYJ, 2FYL, 2KNX, 2KNY
Identifiers
Symbols	LRP1; A2MR; APOER; APR; CD91; FLJ16451; IGFBP3R; LRP; MGC88725; TGFBR5
External IDs	OMIM: 107770 MGI: 96828 HomoloGene: 1744 GeneCards: LRP1 Gene
Gene Ontology
Molecular function	• protease binding; • receptor activity; • calcium ion binding; • protein binding; • protein complex binding; • apolipoprotein binding; • apolipoprotein E binding; • lipoprotein transporter activity; • lipoprotein particle receptor binding;
Cellular component	• membrane fraction; • nucleus; • cytoplasm; • endosome; • plasma membrane; • integral to plasma membrane; • coated pit; • clathrin-coated vesicle; • dendrite; • neuronal cell body;
Biological process	• receptor-mediated endocytosis; • activation of protein kinase C activity by G-protein coupled receptor protein signaling pathway; • multicellular organismal development; • aging; • cell proliferation; • positive regulation of cholesterol efflux; • negative regulation of Wnt receptor signaling pathway; • positive regulation of lipid transport; • regulation of cholesterol transport; • regulation of phospholipase A2 activity; • lipoprotein metabolic process; • lipoprotein transport; • apoptotic cell clearance; • positive regulation of anti-apoptosis;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs

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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.^[1]^[2]

[edit] LRP1 and Alzheimer's disease

Neurons require cholesterol to function. Cholesterol is imported into the neuron by the apolipoprotein apoE4 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.^[3]

[edit] Interactions

LRP1 has been shown to interact with Apolipoprotein E,^[4]^[5] Lipoprotein lipase,^[6]^[7]^[8] Urokinase receptor,^[9] MAPK8IP2,^[10] Tissue plasminogen activator,^[11]^[12] Thrombospondin 1,^[13]^[14]^[15] SYNJ2BP,^[10] DLG4,^[10] NOS1AP,^[10] Calcitonin receptor,^[16] APBB1,^[17] ITGB1BP1,^[10] MAPK8IP1,^[10] GIPC1^[10] and SHC1.^[18]^[19]

[edit] Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^[20]

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Statin Pathway edit

[edit] See also

[edit] References

^ Herz J, Hamann U, Rogne S, Myklebost O, Gausepohl H, Stanley KK (December 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". EMBO J. 7 (13): 4119–27. PMC 455121. PMID 3266596. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=455121.
^ Myklebost O, Arheden K, Rogne S, Geurts van Kessel A, Mandahl N, Herz J, Stanley K, Heim S, Mitelman F (July 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.
^ Liu Q, Zerbinatti CV, Zhang J, Hoe HS, Wang B, Cole SL, Herz J, Muglia L, Bu G. et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2045076.
^ . PMID 277965.
^ Kowal RC, Herz J, Goldstein JL, Esser V, Brown MS (August 1989). "Low density lipoprotein receptor-related protein mediates uptake of cholesteryl esters derived from apoprotein E-enriched lipoproteins". Proc. Natl. Acad. Sci. U.S.A. 86 (15): 5810–4. PMC 297720. PMID 2762297. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=297720.
^ Williams, S E; Inoue I, Tran H, Fry G L, Pladet M W, Iverius P H, Lalouel J M, Chappell D A, Strickland D K (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". J. Biol. Chem. (UNITED STATES) 269 (12): 8653–8. ISSN 0021-9258. 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". J. Biol. Chem. (UNITED STATES) 269 (50): 31747–55. ISSN 0021-9258. PMID 7989348.
^ Chappell, D A; Fry G L, Waknitz M A, Iverius P H, Williams S E, Strickland D K (Dec. 1992). "The low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor binds and mediates catabolism of bovine milk lipoprotein lipase". J. Biol. Chem. (UNITED STATES) 267 (36): 25764–7. ISSN 0021-9258. PMID 1281473.
^ Czekay, R P; Kuemmel T A, Orlando R A, Farquhar M G (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". Mol. Biol. Cell (United States) 12 (5): 1467–79. ISSN 1059-1524. PMC 34598. PMID 11359936. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=34598.
^ ^a ^b ^c ^d ^e ^f ^g Gotthardt, M; Trommsdorff M, Nevitt M F, Shelton J, Richardson J A, 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". J. Biol. Chem. (UNITED STATES) 275 (33): 25616–24. doi:10.1074/jbc.M000955200. ISSN 0021-9258. PMID 10827173.
^ Zhuo, M; Holtzman D M, Li Y, Osaka H, DeMaro J, Jacquin M, Bu G (Jan. 2000). "Role of tissue plasminogen activator receptor LRP in hippocampal long-term potentiation". J. Neurosci. (UNITED STATES) 20 (2): 542–9. PMID 10632583.
^ Orth, K; Madison E L, Gething M J, Sambrook J F, 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". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 89 (16): 7422–6. doi:10.1073/pnas.89.16.7422. ISSN 0027-8424. PMC 49722. PMID 1502153. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=49722.
^ Wang, Shuxia; Herndon Mary E, Ranganathan Sripriya, Godyna Svetlana, Lawler Jack, Argraves W Scott, Liau Gene (Mar. 2004). "Internalization but not binding of thrombospondin-1 to low density lipoprotein receptor-related protein-1 requires heparan sulfate proteoglycans". J. Cell. Biochem. (United States) 91 (4): 766–76. doi:10.1002/jcb.10781. ISSN 0730-2312. PMID 14991768.
^ Mikhailenko, I; Krylov D, Argraves K M, Roberts D D, Liau G, Strickland D K (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". J. Biol. Chem. (UNITED STATES) 272 (10): 6784–91. doi:10.1074/jbc.272.10.6784. ISSN 0021-9258. PMID 9045712.
^ Godyna, S; Liau G, Popa I, Stefansson S, Argraves W S (Jun. 1995). "Identification of the low density lipoprotein receptor-related protein (LRP) as an endocytic receptor for thrombospondin-1". J. Cell Biol. (UNITED STATES) 129 (5): 1403–10. doi:10.1083/jcb.129.5.1403. ISSN 0021-9525. PMC 2120467. PMID 7775583. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2120467.
^ Orr, Anthony Wayne; Pedraza Claudio E, Pallero Manuel Antonio, Elzie Carrie A, Goicoechea Silvia, Strickland Dudley K, Murphy-Ullrich Joanne E (Jun. 2003). "Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly". J. Cell Biol. (United States) 161 (6): 1179–89. doi:10.1083/jcb.200302069. ISSN 0021-9525. PMC 2172996. PMID 12821648. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2172996.
^ Trommsdorff, M; Borg J P, Margolis B, Herz J (Dec. 1998). "Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein". J. Biol. Chem. (UNITED STATES) 273 (50): 33556–60. doi:10.1074/jbc.273.50.33556. ISSN 0021-9258. PMID 9837937.
^ Barnes, Helen; Ackermann Elizabeth J, van der Geer Peter (Jun. 2003). "v-Src induces Shc binding to tyrosine 63 in the cytoplasmic domain of the LDL receptor-related protein 1". Oncogene (England) 22 (23): 3589–97. doi:10.1038/sj.onc.1206504. ISSN 0950-9232. PMID 12789267.
^ Loukinova, Elena; Ranganathan Sripriya, Kuznetsov Sergey, Gorlatova Natalia, Migliorini Mary M, Loukinov Dmitri, Ulery Paula G, Mikhailenko Irina, Lawrence Daniel A, Strickland Dudley K (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". J. Biol. Chem. (United States) 277 (18): 15499–506. doi:10.1074/jbc.M200427200. ISSN 0021-9258. PMID 11854294.
^ The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430". http://www.wikipathways.org/index.php/Pathway:WP430.

[edit] Further reading

Li Z, Dai J, Zheng H, et al. (2002). "An integrated view of the roles and mechanisms of heat shock protein gp96-peptide complex in eliciting immune response.". Front. Biosci. 7: d731–51. PMID 11861214.
van der Geer P (2002). "Phosphorylation of LRP1: regulation of transport and signal transduction.". Trends Cardiovasc. Med. 12 (4): 160–5. doi:10.1016/S1050-1738(02)00154-8. PMID 12069755.
May P, Herz J (2004). "LDL receptor-related proteins in neurodevelopment.". Traffic 4 (5): 291–301. doi:10.1034/j.1600-0854.2003.00086_4_5.x. PMID 12713657.
Llorente-Cortés V, Badimon L (2005). "LDL receptor-related protein and the vascular wall: implications for atherothrombosis.". Arterioscler. Thromb. Vasc. Biol. 25 (3): 497–504. doi:10.1161/01.ATV.0000154280.62072.fd. PMID 15705932.
Huang SS, Huang JS (2005). "TGF-beta control of cell proliferation.". J. Cell. Biochem. 96 (3): 447–62. doi:10.1002/jcb.20558. PMID 16088940.
Lillis AP, Mikhailenko I, Strickland DK (2005). "Beyond endocytosis: LRP function in cell migration, proliferation and vascular permeability.". J. Thromb. Haemost. 3 (8): 1884–93. doi:10.1111/j.1538-7836.2005.01371.x. PMID 16102056.

[edit] External links

MeSH CD91+Antigen

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[pmid3266596-0] Herz J, Hamann U, Rogne S, Myklebost O, Gausepohl H, Stanley KK (December 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". EMBO J. 7 (13): 4119–27. PMC 455121. PMID 3266596. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=455121.

[pmid2548950-1] Myklebost O, Arheden K, Rogne S, Geurts van Kessel A, Mandahl N, Herz J, Stanley K, Heim S, Mitelman F (July 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.

[2] Liu Q, Zerbinatti CV, Zhang J, Hoe HS, Wang B, Cole SL, Herz J, Muglia L, Bu G. et al. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2045076.

[3] . PMID 277965.

[4] Kowal RC, Herz J, Goldstein JL, Esser V, Brown MS (August 1989). "Low density lipoprotein receptor-related protein mediates uptake of cholesteryl esters derived from apoprotein E-enriched lipoproteins". Proc. Natl. Acad. Sci. U.S.A. 86 (15): 5810–4. PMC 297720. PMID 2762297. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=297720.

[pmid7510694-5] Williams, S E; Inoue I, Tran H, Fry G L, Pladet M W, Iverius P H, Lalouel J M, Chappell D A, Strickland D K (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". J. Biol. Chem. (UNITED STATES) 269 (12): 8653–8. ISSN 0021-9258. PMID 7510694.

[pmid7989348-6] 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". J. Biol. Chem. (UNITED STATES) 269 (50): 31747–55. ISSN 0021-9258. PMID 7989348.

[pmid1281473-7] Chappell, D A; Fry G L, Waknitz M A, Iverius P H, Williams S E, Strickland D K (Dec. 1992). "The low density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor binds and mediates catabolism of bovine milk lipoprotein lipase". J. Biol. Chem. (UNITED STATES) 267 (36): 25764–7. ISSN 0021-9258. PMID 1281473.

[pmid11359936-8] Czekay, R P; Kuemmel T A, Orlando R A, Farquhar M G (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". Mol. Biol. Cell (United States) 12 (5): 1467–79. ISSN 1059-1524. PMC 34598. PMID 11359936. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=34598.

[pmid10827173-9] ^ ^a ^b ^c ^d ^e ^f ^g Gotthardt, M; Trommsdorff M, Nevitt M F, Shelton J, Richardson J A, 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". J. Biol. Chem. (UNITED STATES) 275 (33): 25616–24. doi:10.1074/jbc.M000955200. ISSN 0021-9258. PMID 10827173.

[pmid10632583-10] Zhuo, M; Holtzman D M, Li Y, Osaka H, DeMaro J, Jacquin M, Bu G (Jan. 2000). "Role of tissue plasminogen activator receptor LRP in hippocampal long-term potentiation". J. Neurosci. (UNITED STATES) 20 (2): 542–9. PMID 10632583.

[pmid1502153-11] Orth, K; Madison E L, Gething M J, Sambrook J F, 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". Proc. Natl. Acad. Sci. U.S.A. (UNITED STATES) 89 (16): 7422–6. doi:10.1073/pnas.89.16.7422. ISSN 0027-8424. PMC 49722. PMID 1502153. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=49722.

[pmid14991768-12] Wang, Shuxia; Herndon Mary E, Ranganathan Sripriya, Godyna Svetlana, Lawler Jack, Argraves W Scott, Liau Gene (Mar. 2004). "Internalization but not binding of thrombospondin-1 to low density lipoprotein receptor-related protein-1 requires heparan sulfate proteoglycans". J. Cell. Biochem. (United States) 91 (4): 766–76. doi:10.1002/jcb.10781. ISSN 0730-2312. PMID 14991768.

[pmid9045712-13] Mikhailenko, I; Krylov D, Argraves K M, Roberts D D, Liau G, Strickland D K (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". J. Biol. Chem. (UNITED STATES) 272 (10): 6784–91. doi:10.1074/jbc.272.10.6784. ISSN 0021-9258. PMID 9045712.

[pmid7775583-14] Godyna, S; Liau G, Popa I, Stefansson S, Argraves W S (Jun. 1995). "Identification of the low density lipoprotein receptor-related protein (LRP) as an endocytic receptor for thrombospondin-1". J. Cell Biol. (UNITED STATES) 129 (5): 1403–10. doi:10.1083/jcb.129.5.1403. ISSN 0021-9525. PMC 2120467. PMID 7775583. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2120467.

[pmid12821648-15] Orr, Anthony Wayne; Pedraza Claudio E, Pallero Manuel Antonio, Elzie Carrie A, Goicoechea Silvia, Strickland Dudley K, Murphy-Ullrich Joanne E (Jun. 2003). "Low density lipoprotein receptor-related protein is a calreticulin coreceptor that signals focal adhesion disassembly". J. Cell Biol. (United States) 161 (6): 1179–89. doi:10.1083/jcb.200302069. ISSN 0021-9525. PMC 2172996. PMID 12821648. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2172996.

[pmid9837937-16] Trommsdorff, M; Borg J P, Margolis B, Herz J (Dec. 1998). "Interaction of cytosolic adaptor proteins with neuronal apolipoprotein E receptors and the amyloid precursor protein". J. Biol. Chem. (UNITED STATES) 273 (50): 33556–60. doi:10.1074/jbc.273.50.33556. ISSN 0021-9258. PMID 9837937.

[pmid12789267-17] Barnes, Helen; Ackermann Elizabeth J, van der Geer Peter (Jun. 2003). "v-Src induces Shc binding to tyrosine 63 in the cytoplasmic domain of the LDL receptor-related protein 1". Oncogene (England) 22 (23): 3589–97. doi:10.1038/sj.onc.1206504. ISSN 0950-9232. PMID 12789267.

[pmid11854294-18] Loukinova, Elena; Ranganathan Sripriya, Kuznetsov Sergey, Gorlatova Natalia, Migliorini Mary M, Loukinov Dmitri, Ulery Paula G, Mikhailenko Irina, Lawrence Daniel A, Strickland Dudley K (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". J. Biol. Chem. (United States) 277 (18): 15499–506. doi:10.1074/jbc.M200427200. ISSN 0021-9258. PMID 11854294.

[WikiPathways-19] The interactive pathway map can be edited at WikiPathways: "Statin_Pathway_WP430". http://www.wikipathways.org/index.php/Pathway:WP430.

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LRP1

Contents

[edit] LRP1 and Alzheimer's disease

[edit] Interactions

[edit] Interactive pathway map

[edit] See also

[edit] References

[edit] Further reading

[edit] External links

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