Tyrosine phosphorylation of HPK1 by activated Src promotes ischemic brain injury in rat hippocampal CA1 region.
FEBS Lett
; 582(13): 1894-900, 2008 Jun 11.
Article
em En
| MEDLINE
| ID: mdl-18498770
ABSTRACT
Hematopoietic progenitor kinase 1 (HPK1) is a hematopoietic cell-restricted member of the Ste20 serine/threonine kinase super family. We recently reported that HPK1 is involved in c-Jun NH2-terminal kinase (JNK) signaling pathway by sequential activation of MLK3-MKK7-JNK3 after cerebral ischemia. Here, we used 4-amino-5-(4-chlorophenyl)-7-(t-butyl) pyrazolo [3,4-d] pyrimidine (PP2) and MK801 to investigate the events upstream of HPK1 in ischemic brain injury. Immunoprecipitation and immunoblot results showed that PP2 and MK801 significantly decreased the activation of Src, HPK1, MLK3, JNK3 and c-Jun, respectively, during ischemia/reperfusion. Histology and TUNEL staining showed PP2 or MK801 protects against neuron death after brain ischemia. We speculate that this unique signaling pathway through the tyrosine phosphorylation of HPK1 promotes ischemic brain injury by activated Src via N-methyl-d-aspartate receptor and, ultimately, the activation of the MLK3-MKK7-JNK3 pathway after cerebral ischemia.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tirosina
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Isquemia Encefálica
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Proteínas Serina-Treonina Quinases
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Quinases da Família src
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Hipocampo
Limite:
Animals
Idioma:
En
Revista:
FEBS Lett
Ano de publicação:
2008
Tipo de documento:
Article