Source:http://linkedlifedata.com/resource/pubmed/id/17620336
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
36
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| pubmed:dateCreated |
2007-9-3
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| pubmed:abstractText |
Insulin-like growth factor types 1 and 2 (IGF-1; IGF-2) and insulin-like peptides are all members of the insulin superfamily of peptide hormones but bind to several distinct classes of membrane receptor. Like the insulin receptor, the IGF-1 receptor is a heterotetrameric receptor tyrosine kinase, whereas the IGF-2/ mannose 6-phosphate receptor is a single transmembrane domain protein that is thought to function primarily as clearance receptors. We recently reported that IGF-1 and IGF-2 stimulate the ERK1/2 cascade by triggering sphingosine kinase-dependent "transactivation" of G protein-coupled sphingosine-1-phosphate receptors. To determine which IGF receptors mediate this effect, we tested seven insulin family peptides, IGF-1, IGF-2, insulin, and insulin-like peptides 3, 4, 6, and 7, for the ability to activate ERK1/2 in HEK293 cells. Only IGF-1 and IGF-2 potently activated ERK1/2. Although IGF-2 was predictably less potent than IGF-1 in activating the IGF-1 receptor, they were equipotent stimulators of ERK1/2. Knockdown of IGF-1 receptor expression by RNA interference reduced the IGF-1 response to a greater extent than the IGF-2 response, suggesting that IGF-2 did not signal exclusively via the IGF-1 receptor. In contrast, IGF-2 receptor knockdown markedly reduced IGF-2-stimulated ERK1/2 phosphorylation, with no effect on the IGF-1 response. As observed previously, both the IGF-1 and the IGF-2 responses were sensitive to pertussis toxin and the sphingosine kinase inhibitor, dimethylsphingosine. These data indicate that endogenous IGF-1 and IGF-2 receptors can independently initiate ERK1/2 signaling and point to a potential physiologic role for IGF-2 receptors in the cellular response to IGF-2.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/IGF2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor I,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin-Like Growth Factor II,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotransferases (Alcohol Group...,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, IGF Type 1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, IGF Type 2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Lysosphingolipid,
http://linkedlifedata.com/resource/pubmed/chemical/sphingosine kinase
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| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
7
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| pubmed:volume |
282
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
26150-7
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:17620336-Cell Line,
pubmed-meshheading:17620336-Enzyme Activation,
pubmed-meshheading:17620336-Humans,
pubmed-meshheading:17620336-Insulin,
pubmed-meshheading:17620336-Insulin-Like Growth Factor I,
pubmed-meshheading:17620336-Insulin-Like Growth Factor II,
pubmed-meshheading:17620336-MAP Kinase Signaling System,
pubmed-meshheading:17620336-Mitogen-Activated Protein Kinase 1,
pubmed-meshheading:17620336-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:17620336-Phosphorylation,
pubmed-meshheading:17620336-Phosphotransferases (Alcohol Group Acceptor),
pubmed-meshheading:17620336-Proteins,
pubmed-meshheading:17620336-RNA Interference,
pubmed-meshheading:17620336-Receptor, IGF Type 1,
pubmed-meshheading:17620336-Receptor, IGF Type 2,
pubmed-meshheading:17620336-Receptors, Lysosphingolipid
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| pubmed:year |
2007
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| pubmed:articleTitle |
The insulin-like growth factor type 1 and insulin-like growth factor type 2/mannose-6-phosphate receptors independently regulate ERK1/2 activity in HEK293 cells.
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| pubmed:affiliation |
Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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