|
rdf:type |
|
|
lifeskim:mentions |
umls-concept:C0010453,
umls-concept:C0021469,
umls-concept:C0027882,
umls-concept:C0220839,
umls-concept:C0282625,
umls-concept:C0285558,
umls-concept:C0812228,
umls-concept:C1150423,
umls-concept:C1150587,
umls-concept:C1366765,
umls-concept:C1367731,
umls-concept:C1533157,
umls-concept:C1705328,
umls-concept:C1705341,
umls-concept:C1705632,
umls-concept:C1710082
|
|
pubmed:issue |
5
|
|
pubmed:dateCreated |
2004-3-10
|
|
pubmed:abstractText |
Glutamate receptor activation of mitogen-activated protein (MAP) kinase signalling cascades has been implicated in diverse neuronal functions such as synaptic plasticity, development and excitotoxicity. We have previously shown that Ca2+-influx through NMDA receptors in cultured striatal neurones mediates the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt/protein kinase B (PKB) through a phosphatidylinositol 3-kinase (PI 3-kinase)-dependent pathway. Exposing neurones to the Src family tyrosine kinase inhibitor PP2, but not the inactive analogue PP3, inhibited NMDA receptor-induced phosphorylation of ERK1/2 and Akt/PKB in a concentration-dependent manner, and reduced cAMP response element-binding protein (CREB) phosphorylation. To establish a link between Src family tyrosine kinase-mediated phosphorylation and PI 3-kinase signalling, affinity precipitation experiments were performed with the SH2 domains of the PI 3-kinase regulatory subunit p85. This revealed a Src-dependent phosphorylation of a focal adhesion kinase (FAK)-p85 complex on glutamate stimulation. Demonstrating that PI3-kinase is not ubiquitously involved in NMDA receptor signal transduction, the PI 3-kinase inhibitors wortmannin and LY294002 did not prevent NMDA receptor Ca2+-dependent phosphorylation of c-Jun N-terminal kinase 1/2 (JNK1/2). Further, inhibiting Src family kinases increased NMDA receptor-dependent JNK1/2 phosphorylation, suggesting that Src family kinase-dependent cascades may physiologically limit signalling to JNK. These results demonstrate that Src family tyrosine kinases and PI3-kinase are pivotal regulators of NMDA receptor signalling to ERK/Akt and JNK in striatal neurones.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP Response...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Kinase 1,
http://linkedlifedata.com/resource/pubmed/chemical/Focal Adhesion Protein-Tyrosine...,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Ptk2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate,
http://linkedlifedata.com/resource/pubmed/chemical/src-Family Kinases
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Mar
|
|
pubmed:issn |
0022-3042
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
88
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1127-39
|
|
pubmed:dateRevised |
2010-11-18
|
|
pubmed:meshHeading |
pubmed-meshheading:15009668-Animals,
pubmed-meshheading:15009668-Calcium,
pubmed-meshheading:15009668-Cells, Cultured,
pubmed-meshheading:15009668-Corpus Striatum,
pubmed-meshheading:15009668-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:15009668-Enzyme Inhibitors,
pubmed-meshheading:15009668-Focal Adhesion Kinase 1,
pubmed-meshheading:15009668-Focal Adhesion Protein-Tyrosine Kinases,
pubmed-meshheading:15009668-Glutamic Acid,
pubmed-meshheading:15009668-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:15009668-Mice,
pubmed-meshheading:15009668-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15009668-Neurons,
pubmed-meshheading:15009668-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:15009668-Phosphorylation,
pubmed-meshheading:15009668-Protein Structure, Tertiary,
pubmed-meshheading:15009668-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15009668-Protein-Tyrosine Kinases,
pubmed-meshheading:15009668-Proto-Oncogene Proteins,
pubmed-meshheading:15009668-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15009668-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:15009668-Signal Transduction,
pubmed-meshheading:15009668-src-Family Kinases
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
Inhibiting Src family tyrosine kinase activity blocks glutamate signalling to ERK1/2 and Akt/PKB but not JNK in cultured striatal neurones.
|
|
pubmed:affiliation |
Centre for Neuroscience Research, GKT School of Biomedical Sciences, King's College London, London, UK.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
