Tyrosine phosphorylation of HPK1 by activated Src promotes ischemic brain injury in rat hippocampal CA1 region

doi:10.1016/j.febslet.2008.05.009

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	Tyrosine phosphorylation of HPK1 by activated Src promotes ischemic brain injury in rat hippocampal CA1 region
	Li, Ting 1,2; Yu, Xiu-Ju 2; Zhang, Guang-Yi 1,2
刊名	FEBS LETTERS
	2008-06-11
卷号	582 期号:13 页码:1894-1900
关键词	HPK1 cerebral ischemia Src N-methyl-D-aspartate receptor (NMDAR) neuroprotection c-jun NH2-terminal kinase (JNK)
ISSN号	0014-5793
DOI	10.1016/j.febslet.2008.05.009
文献子类	Article
英文摘要	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-MWK7-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. (c) 2008 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
WOS关键词	HEMATOPOIETIC PROGENITOR KINASE-1 ; N-TERMINAL KINASE ; ADAPTER PROTEINS ; INHIBITOR ; RECEPTORS ; PATHWAY ; CASCADE ; POTENT ; NR2A ; CRK
WOS研究方向	Biochemistry & Molecular Biology ; Biophysics ; Cell Biology
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000257073800019
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272891]
专题	国家新药筛选中心
通讯作者	Zhang, Guang-Yi
作者单位	1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200231, Peoples R China 2.Xuzhou Med Coll, Jiangsu Key Lab Brain Dis Bioinformat, Res Ctr Biochem & Mol Biol, Jiangsu 221002, Peoples R China;
推荐引用方式 GB/T 7714	Li, Ting,Yu, Xiu-Ju,Zhang, Guang-Yi. Tyrosine phosphorylation of HPK1 by activated Src promotes ischemic brain injury in rat hippocampal CA1 region[J]. FEBS LETTERS,2008,582(13):1894-1900.
APA	Li, Ting,Yu, Xiu-Ju,&Zhang, Guang-Yi.(2008).Tyrosine phosphorylation of HPK1 by activated Src promotes ischemic brain injury in rat hippocampal CA1 region.FEBS LETTERS,582(13),1894-1900.
MLA	Li, Ting,et al."Tyrosine phosphorylation of HPK1 by activated Src promotes ischemic brain injury in rat hippocampal CA1 region".FEBS LETTERS 582.13(2008):1894-1900.