Source:http://linkedlifedata.com/resource/pubmed/id/19595710
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
2009-8-25
|
| pubmed:abstractText |
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by progressive degeneration of motoneurons. We have demonstrated that hepatocyte growth factor (HGF) attenuates loss of both spinal and brainstem motoneurons of ALS model mice expressing mutated human SOD1(G93A) (G93A). This study was designed to assess disease-dependent regulatory mechanisms of c-Met/HGF receptor (c-Met) activation in the facial motoneurons of G93A mice. Using double transgenic mice expressing HGF and mutated SOD1(G93A) (G93A/HGF), we showed that phosphorylation of c-Met tyrosine residues at positions 1230, 1234 and 1235 (phospho-Tyr), and thereby its activation, was slightly evident in G93A and highly obvious in G93A/HGF mice (but absent in WT and HGF-Tg mice). Phosphorylation of the c-Met serine residue at position 985 (phospho-Ser), a residue involved in the negative regulation of its activation, was evident in WT and HGF-Tg mice. Protein phosphatase 2A (PP2A), which is capable of dephosphorylating c-Met phospho-serine, is upregulated in the facial motoneurons of G93A and G93A/HGF mice compared with WT and HGF-Tg mice. Thus, c-Met activation is reciprocally regulated by phosphorylation between c-Met serine and tyrosine residues through PP2A induction in the presence or absence of mutant SOD1 expression, and HGF functions more efficiently in ALS and ALS-related diseases.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Phosphatase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-met,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/superoxide dismutase 1
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Oct
|
| pubmed:issn |
1872-8111
|
| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:volume |
65
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
194-200
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:19595710-Amino Acid Sequence,
pubmed-meshheading:19595710-Amyotrophic Lateral Sclerosis,
pubmed-meshheading:19595710-Animals,
pubmed-meshheading:19595710-Catalytic Domain,
pubmed-meshheading:19595710-Central Nervous System,
pubmed-meshheading:19595710-Disease Models, Animal,
pubmed-meshheading:19595710-Disease Progression,
pubmed-meshheading:19595710-Facial Nerve,
pubmed-meshheading:19595710-Gene Expression Regulation,
pubmed-meshheading:19595710-Hepatocyte Growth Factor,
pubmed-meshheading:19595710-Humans,
pubmed-meshheading:19595710-Mice,
pubmed-meshheading:19595710-Mice, Transgenic,
pubmed-meshheading:19595710-Motor Neurons,
pubmed-meshheading:19595710-Phosphorylation,
pubmed-meshheading:19595710-Protein Phosphatase 2,
pubmed-meshheading:19595710-Proto-Oncogene Proteins c-met,
pubmed-meshheading:19595710-Rhombencephalon,
pubmed-meshheading:19595710-Serine,
pubmed-meshheading:19595710-Superoxide Dismutase,
pubmed-meshheading:19595710-Tyrosine
|
| pubmed:year |
2009
|
| pubmed:articleTitle |
Disease-dependent reciprocal phosphorylation of serine and tyrosine residues of c-Met/HGF receptor contributes disease retardation of a transgenic mouse model of ALS.
|
| pubmed:affiliation |
Division of Molecular Regenerative Medicine, Department of Biochemistry and Molecular Biology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|