Search results for LRP1

Showing 14 results out of 14

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Species

Types

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Protein (5 results from a total of 5)

Identifier: R-HSA-2424272
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: LRP1: Q07954
Identifier: R-HSA-1454844
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: LRP1: Q07954
Identifier: R-HSA-2230981
Species: Homo sapiens
Compartment: endocytic vesicle membrane
Primary external reference: UniProt: Q07954
Identifier: R-HSA-2424260
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: LRP12: Q9Y561
Identifier: R-HSA-2424275
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: LRP10: Q7Z4F1

Interactor (2 results from a total of 2)

Identifier: Q07954-2
Species: Homo sapiens
Primary external reference: UniProt: Q07954-2
Identifier: Q9NZR2
Species: Homo sapiens
Primary external reference: UniProt: Q9NZR2

Reaction (4 results from a total of 4)

Identifier: R-HSA-2168897
Species: Homo sapiens
Compartment: extracellular region, plasma membrane
Once formed in the plasma, the hemopexin:heme complex is rapidly cleared from circulation and it is taken up by the liver (Smith and Morgan 1984, Smith and Morgan 1985, Tolosano et al. 2010, Vinchi et al. 2008), where heme is degraded by heme oxygenases. In mouse, rat and rabbit several experimental evidences led to the postulation of a specific receptor on hepatocytes with high affinity for the hemopexin:heme complex (Smith and Morgan 1981, Smith and Morgan 1984, Smith et al, 1988, Smith et al., 1991), but such a receptor has not been identified to date. The only known hemopexin:heme receptor is LRP1 (CD91) that is ubiquitously expressed and has a low affinity for the complex. LRP1 is a multi-ligand scavenger receptor, involved in endocytosis in some cells types, for example macrophages, and in signaling in other cell types (reviewed in Boucher and Herz 2011). LRP1 is known to act in the metabolism of lipoprotein and it is expressed in several cell types including macrophages, hepatocytes and neurons. Among several ligands, LRP1 (CD91) can bind the hemopexin:heme complex (Hvidberg et al. 2005).
Identifier: R-HSA-2230983
Species: Homo sapiens
Compartment: endocytic vesicle membrane, plasma membrane
The LRP1:hemopexin:heme complex is endocytosed and the complex is dissociated in lysosomes, leading to heme uptake. Heme is then degraded by heme oxygenases. Whereas LRP1 is subsequently recycled to the plasma membrane, the destiny of hemopexin is controversial. Some studies have suggested that hemopexin can be recycled as an intact molecule to the extracellular milieu (Smith and Morgan, 1979). However, it has also been proposed that following hepatic uptake of heme from hemopexin:heme, varying proportions of the protein are either returned to the circulation or degraded in the liver (Potter et al., 1993). Recently, Hvidberg et al. have shown that most hemopexin is degraded in lysosomes (Hvidberg et al., 2005).
Identifier: R-HSA-5362427
Species: Homo sapiens
Compartment: plasma membrane
The establishment of a signaling gradient of Hh-Np is modulated in part by the interaction of the ligand with heparin sulphate proteoglycans (HSPGs) in the extracellular matrix (ECM) of the secreting cell. Interactions with HSPGs can influence Hh oligomerization and also impact the lateral and long-range spread of Hh ligand (reviewed in Gallet, 2011; Briscoe and Therond, 2013). Interactions with HSPGs can stimulate or restrict Hh signaling depending on the context and the particular proteoglycans involved (see for instance Witt et al, 2013; Li et al, 2011; Capurro et al, 2005; Capurro et al, 2012; reviewed in Gallet, 2011).

In vertebrate cells, the GPI-anchored HSPG glypican 5 (GPC5) has been shown to stimulate Hh signaling by promoting the interaction between SHH ligand and the PTCH1 receptor (Li et al, 2011; Witt et al, 2013). SHH and PTCH1 binding depends on the GAG chains of GPC5, as versions lacking the GAG insertion sites are compromised for both ligand and receptor binding, and these proteins do not stimulate Hh signaling (Li et al, 2011). Amplification of GPC5 has been observed in 20% of rhabdomyosarcomas (Williamson et al, 2007), and aberrant activation of Hh signaling in these cells promotes cellular proliferation (Li et al, 2011).
Identifier: R-HSA-1454781
Species: Homo sapiens
Compartment: extracellular region
Alpha 2-macroglobulin (A2M) is a plasma glycoprotein consisting of 4 near-identical subunits (Andersen et al. 1995). A2M inhibits almost all endopeptidases regardless of their specificities (Barrett 1981). A2M binding to an endopeptidase is triggered by cleavage of a peptide bond in the 'bait region' of A2M, triggering a conformational change in A2M that in turn entraps the peptidase without blocking the active site (Barrett & Starkey 1973). This blocks enzyme activity against large protein substrates while not preventing activity on low molecular weight substrates.

Once bound, A2M-proteinase complexes are endocytosed by low density lipoprotein receptor-related protein-1 (LRP1) (Strickland et al. 1990).

Active metalloproteinases (MMPs) that can be entrapped by A2M include MMP3 (Enghild et al. 1989) MMP1 (Grinnell et al. 1998) and MMP 13 (Beekman et al. 1999).

The significance of this mechanism as a regulator of MMP activity is unclear (Baker et al. 2002, Nagase et al. 2006).

Complex (2 results from a total of 2)

Identifier: R-HSA-2168892
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-2230986
Species: Homo sapiens
Compartment: endocytic vesicle membrane

Pathway (1 results from a total of 1)

Identifier: R-HSA-2168880
Species: Homo sapiens
Compartment: extracellular region, endocytic vesicle membrane, plasma membrane
Free heme is damaging to tissues as it intercalates into biologic membranes, perturbing lipid bilayers and promoting the conversion of low-density lipoprotein to cytotoxic oxidized products. Moreover, it represents a source of redox-active iron that, participating in the Fenton reaction, generates oxygen radicals (reviewed in Gutteridge 1989). Free heme in plasma is mainly generated from hemoglobin released by circulating erythrocytes in pathologic conditions associated with intravascular hemolysis. Free hemoglobin in plasma is scavenged by the extracellular protein haptoglobin. Haptoglobin is produced by the liver and secreted into the plasma. Haptoglobin binds dimers of hemoglobin subunits rather than the intact tetramer (reviewed in Nielsen et al. 2010, Levy et al. 2010, Ascenzi et al. 2005, Madsen et al. 2001). The resulting haptoglobin:hemoglobin complex is then bound by CD163, expressed on plasma membranes of monocytes and macrophages, and endocytosed. When the buffering capacity of plasma haptoglobin is overwhelmed, heme is released from methemoglobin and it is bound by albumin and then transferred to hemopexin (reviewed in Chiabrando et al. 2011, Nielsen et al. 2010, Tolosano et al. 2010, Ascenzi et al. 2005, Tolosano and Altruda 2002). Hemopexin is produced mainly in the liver. Once secreted into the plasma, hemopexin binds heme and the hemopexin:heme complex is then preferentially delivered to liver hepatocytes, bound by LRP1 (CD91) and endocytosed.
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