TY - JOUR
T1 - Signaling through LRP1
T2 - Protection from atherosclerosis and beyond
AU - Boucher, Philippe
AU - Herz, Joachim
N1 - Funding Information:
This work was supported by grants from, Centre National pour la Recherche Scientifique (CNRS) , University of Strasbourg , Fondation de France , Agence Nationale de la Recherche ( ANR-06-PHYSIO-032-01 , and ANR-09-BLAN-0121-01 ), the National Institutes of Health, the American Health Assistance Foundation, the Perot Family Foundation, The Consortium for Frontotemporal Dementia Research (CFR) and the Wolfgang-Paul Program of the Humboldt Foundation.
PY - 2011/1/1
Y1 - 2011/1/1
N2 - The low-density lipoprotein receptor-related protein (LRP1) is a multifunctional cell surface receptor that belongs to the LDL receptor (LDLR) gene family and that is widely expressed in several tissues. LRP1 consists of an 85-kDa membrane-bound carboxyl fragment (β chain) and a non-covalently attached 515-kDa (α chain) amino-terminal fragment. Through its extracellular domain, LRP1 binds at least 40 different ligands ranging from lipoprotein and protease inhibitor complex to growth factors and extracellular matrix proteins. LRP-1 has also been shown to interact with scaffolding and signaling proteins via its intracellular domain in a phosphorylation-dependent manner and to function as a co-receptor partnering with other cell surface or integral membrane proteins. LRP-1 is thus implicated in two major physiological processes: endocytosis and regulation of signaling pathways, which are both involved in diverse biological roles including lipid metabolism, cell growth/differentiation processes, degradation of proteases, and tissue invasion. The embryonic lethal phenotype obtained after target disruption of the LRP-1 gene in the mouse highlights the biological importance of this receptor and revealed a critical, but yet undefined role in development. Tissue-specific gene deletion studies also reveal an important contribution of LRP1 in vascular remodeling, foam cell biology, the central nervous system, and in the molecular mechanisms of atherosclerosis.
AB - The low-density lipoprotein receptor-related protein (LRP1) is a multifunctional cell surface receptor that belongs to the LDL receptor (LDLR) gene family and that is widely expressed in several tissues. LRP1 consists of an 85-kDa membrane-bound carboxyl fragment (β chain) and a non-covalently attached 515-kDa (α chain) amino-terminal fragment. Through its extracellular domain, LRP1 binds at least 40 different ligands ranging from lipoprotein and protease inhibitor complex to growth factors and extracellular matrix proteins. LRP-1 has also been shown to interact with scaffolding and signaling proteins via its intracellular domain in a phosphorylation-dependent manner and to function as a co-receptor partnering with other cell surface or integral membrane proteins. LRP-1 is thus implicated in two major physiological processes: endocytosis and regulation of signaling pathways, which are both involved in diverse biological roles including lipid metabolism, cell growth/differentiation processes, degradation of proteases, and tissue invasion. The embryonic lethal phenotype obtained after target disruption of the LRP-1 gene in the mouse highlights the biological importance of this receptor and revealed a critical, but yet undefined role in development. Tissue-specific gene deletion studies also reveal an important contribution of LRP1 in vascular remodeling, foam cell biology, the central nervous system, and in the molecular mechanisms of atherosclerosis.
KW - Atherosclerosis
KW - Cell signaling
KW - LRP1
KW - Lipid metabolism
KW - Vascular smooth muscle cells
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U2 - 10.1016/j.bcp.2010.09.018
DO - 10.1016/j.bcp.2010.09.018
M3 - Comment/debate
C2 - 20920479
AN - SCOPUS:78549255860
SN - 0006-2952
VL - 81
SP - 1
EP - 5
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 1
ER -