Source:http://linkedlifedata.com/resource/pubmed/id/17064357
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
5
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| pubmed:dateCreated |
2006-11-19
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| pubmed:abstractText |
Extracellular signal-regulated kinase (ERK), a member of the mitogen-activated protein kinase pathway, has been increasingly implicated in the pathogenesis of Alzheimer's disease due to its critical role in brain function. While we previously demonstrated that ERK is activated in Alzheimer's disease, the upstream cascade leading to its activation had not been fully examined. In this study, we focused on Raf-1, one of the physiological activators of the ERK pathway. Raf-1 is activated by phosphorylation at Ser338 and Tyr340/341 and inhibited by phosphorylation at Ser259. Interestingly, phosphorylation at all three sites on Raf-1 was increased as evidenced by both immunocytochemistry and immunoblot analysis in Alzheimer's disease brains compared to age-matched controls. Both phospho-Raf-1 (Ser259) and phospho-Raf-1 (Ser338) were localized to intracytoplasmic granular structures, whereas phospho-Raf-1 (Tyr340/341) was localized to neurofibrillary tangles and granules in pyramidal neurons in Alzheimer's disease hippocampus. There is extensive overlap between phospho-Raf-1 (Ser338) and phospho-Mek1/2, the downstream effector of Raf-1, suggestive of a mechanistic link. Additionally, increased levels of Raf-1 are associated with Ras and MEK1 in Alzheimer's disease as evidenced by its coimmunoprecipitation with Ras and Mek1, respectively. Based on these findings, we speculate that Raf-1 is activated to effectively mediate Ras-dependent signals in Alzheimer's disease.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Biological Markers,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/MAP Kinase Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/MAP2K1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-raf,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
0022-3042
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
99
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1377-88
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:17064357-Aged,
pubmed-meshheading:17064357-Aged, 80 and over,
pubmed-meshheading:17064357-Alzheimer Disease,
pubmed-meshheading:17064357-Amino Acid Sequence,
pubmed-meshheading:17064357-Biological Markers,
pubmed-meshheading:17064357-Brain,
pubmed-meshheading:17064357-Cytoplasmic Granules,
pubmed-meshheading:17064357-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:17064357-Hippocampus,
pubmed-meshheading:17064357-Humans,
pubmed-meshheading:17064357-Immunohistochemistry,
pubmed-meshheading:17064357-MAP Kinase Kinase 1,
pubmed-meshheading:17064357-MAP Kinase Signaling System,
pubmed-meshheading:17064357-Neurofibrillary Tangles,
pubmed-meshheading:17064357-Phosphorylation,
pubmed-meshheading:17064357-Proto-Oncogene Proteins c-raf,
pubmed-meshheading:17064357-Pyramidal Cells,
pubmed-meshheading:17064357-Serine,
pubmed-meshheading:17064357-Signal Transduction,
pubmed-meshheading:17064357-Tyrosine,
pubmed-meshheading:17064357-Up-Regulation,
pubmed-meshheading:17064357-ras Proteins
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| pubmed:year |
2006
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| pubmed:articleTitle |
Distribution, levels and phosphorylation of Raf-1 in Alzheimer's disease.
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| pubmed:affiliation |
Department of Pathology, Case Western Reserve University, and MetroHealth Medical Center, Cleveland, Ohio 44106, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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