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rdf:type |
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lifeskim:mentions |
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pubmed:dateCreated |
1999-1-26
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pubmed:abstractText |
The low-density-lipoprotein-receptor-related protein (LRP) binds and internalizes numerous ligands, including lipoproteins, proteinase-inhibitor complexes and others. We have shown previously that LRP-mediated ligand internalization is dependent on cAMP-dependent protein kinase (PKA) activity. Here, we investigated whether ligation of LRP increases the intracellular cAMP level and PKA activity via a stimulatory GTP-binding protein. Treatment of LRP-expressing cell lines with the LRP ligands lactoferrin or urokinase-type plasminogen activator caused a significant elevation in cAMP and stimulated PKA activity in a dose-dependent manner. Addition of the 39 kDa receptor-associated protein (RAP), an antagonist for ligand interactions with LRP, blocked the lactoferrin-induced increase in PKA activity, demonstrating a requirement for ligand binding to LRP. Incubation of cell membrane fractions with lactoferrin increased GTPase activity in a time- and dose-dependent manner, and treatment with LRP ligands suppressed cholera-toxin-mediated ADP-ribosylation of the Gsalpha subunit of a heterotrimeric G-protein. Affinity precipitation of LRP with RAP resulted in co-precipitation of two isoforms of Gsalpha from detergent extracts. We thus conclude that LRP is a signalling receptor that associates directly with a stimulatory heterotrimeric G-protein and activates a downstream PKA-dependent pathway.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-1371121,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-1493332,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-15335994,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-1645724,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-188466,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-2170379,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-2303711,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-2881559,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-7508685,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-7513689,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-7518427,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-7520911,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-7543026,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-7568158,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-7589986,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-7615159,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-7681282,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-7721883,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-7944146,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-7979258,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-8034609,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-8045932,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-8161545,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-8280459,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-8363571,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-8380222,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-8548817,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-8626788,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-8654360,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-8970738,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-9003044,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-9038141,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-9045716,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-9217325,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-9243514,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-9252378,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-9277131,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-9316499,
http://linkedlifedata.com/resource/pubmed/commentcorrection/9820815-9449704
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cholera Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/GTP Phosphohydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Lactoferrin,
http://linkedlifedata.com/resource/pubmed/chemical/Low Density Lipoprotein...,
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Immunologic
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0264-6021
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
336 ( Pt 2)
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
381-6
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:9820815-Cholera Toxin,
pubmed-meshheading:9820815-Cyclic AMP,
pubmed-meshheading:9820815-Cyclic AMP-Dependent Protein Kinases,
pubmed-meshheading:9820815-GTP Phosphohydrolases,
pubmed-meshheading:9820815-GTP-Binding Protein alpha Subunits, Gs,
pubmed-meshheading:9820815-GTP-Binding Proteins,
pubmed-meshheading:9820815-Humans,
pubmed-meshheading:9820815-Lactoferrin,
pubmed-meshheading:9820815-Low Density Lipoprotein Receptor-Related Protein-1,
pubmed-meshheading:9820815-Plasminogen Activator Inhibitor 1,
pubmed-meshheading:9820815-Receptors, Immunologic,
pubmed-meshheading:9820815-Signal Transduction
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pubmed:year |
1998
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pubmed:articleTitle |
Low-density-lipoprotein-receptor-related protein (LRP) interacts with a GTP-binding protein.
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pubmed:affiliation |
The Scripps Research Institute, Department of Immunology, 10550 N. Torrey Pines Road, IMM13, La Jolla, CA 92037, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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