Tyrosine 402 Phosphorylation of Pyk2 Is Involved in Ionomycin-Induced Neurotransmitter Release

doi:10.1371/journal.pone.0094574

	Tyrosine 402 Phosphorylation of Pyk2 Is Involved in Ionomycin-Induced Neurotransmitter Release
	Zhang, Zhao 2,3,4; Zhang, Yun 2,3,4; Mou, Zheng 2,3,4; Chu, Shifeng 2,3,4; Chen, Xiaoyu 2,3,4; He, Wenbin 1,2,3,4; Guo, Xiaofeng 1; Yuan, Yuhe 2,3,4; Takahashi, Masami 5; Chen, Naihong 2,3,4
刊名	PLOS ONE
	2014-04-09
卷号	9 期号:4
ISSN号	1932-6203
DOI	10.1371/journal.pone.0094574
文献子类	Article
英文摘要	Protein tyrosine kinases, which are highly expressed in the central nervous system, are implicated in many neural processes. However, the relationship between protein tyrosine kinases and neurotransmitter release remains unknown. In this study, we found that ionomycin, a Ca2+ ionophore, concurrently induced asynchronous neurotransmitter release and phosphorylation of a non-receptor protein tyrosine kinase, proline-rich tyrosine kinase 2 (Pyk2), in clonal rat pheochromocytoma PC12 cells and cerebellar granule cells, whereas introduction of Pyk2 siRNA dramatically suppressed ionomycin-induced neurotransmitter release. Further study indicated that Tyr-402 (Y402) in Pyk2, instead of other tyrosine sites, underwent rapid phosphorylation after ionomycin induction in 1 min to 2 min. We demonstrated that the mutant of Pyk2 Y402 could abolish ionomycin-induced dopamine (DA) release by transfecting cells with recombinant Pyk2 and its mutants (Y402F, Y579F, Y580F, and Y881F). In addition, Src inhibition could prolong phosphorylation of Pyk2 Y402 and increase DA release. These findings suggested that Pyk2 was involved in ionomycin-induced neurotransmitter release through phosphorylation of Y402.
资助项目	National Natural Science Foundation of China[81274122] ; National Natural Science Foundation of China[81073078] ; National Natural Science Foundation of China[81001487] ; National Natural Science Foundation of China[81373510] ; National Natural Science Foundation of China[81373998] ; National Natural Science Foundation of China[90713045] ; National Key Sci-Tech Major Special Item[2012ZX09301002-004] ; National Key Sci-Tech Major Special Item[2012ZX09103101-006] ; National 863 Program of China[2012AA020303] ; Program for Changjiang Scholars and Innovative Research Team in University[IRT1007] ; Beijing Natural Science Foundation[7131013] ; Research Fund for the Doctoral Program of Higher Education of China[20121106130001]
WOS关键词	FOCAL ADHESION KINASE ; ACTIVATED PROTEIN-KINASE ; CENTRAL-NERVOUS-SYSTEM ; TRANSMITTER RELEASE ; SYNAPTIC TRANSMISSION ; HIPPOCAMPAL-NEURONS ; CEREBRAL-ISCHEMIA ; SIGNALING EVENTS ; RAT-BRAIN ; CELLS
WOS研究方向	Science & Technology - Other Topics
语种	英语
出版者	PUBLIC LIBRARY SCIENCE
WOS记录号	WOS:000334339000132
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277118]
专题	中国科学院上海药物研究所
通讯作者	Takahashi, Masami
作者单位	1.Shanxi Univ Tradit Chinese Med, Basic Med Coll, Taiyuan, Peoples R China; 2.Chinese Acad Sci, Inst Mat Med, Dept Pharmacol,State Key Lab Bioact Subst & Funct, Beijing Key Lab New Drug Mech & Pharmacol Evaluat, Beijing, Peoples R China; 3.Chinese Acad Sci, Ctr Neurosci, Beijing, Peoples R China; 4.Peking Union Med Coll, Beijing 100021, Peoples R China; 5.Kitasato Univ, Sch Med, Dept Biochem, Sagamihara, Kanagawa 228, Japan
推荐引用方式 GB/T 7714	Zhang, Zhao,Zhang, Yun,Mou, Zheng,et al. Tyrosine 402 Phosphorylation of Pyk2 Is Involved in Ionomycin-Induced Neurotransmitter Release[J]. PLOS ONE,2014,9(4).
APA	Zhang, Zhao.,Zhang, Yun.,Mou, Zheng.,Chu, Shifeng.,Chen, Xiaoyu.,...&Chen, Naihong.(2014).Tyrosine 402 Phosphorylation of Pyk2 Is Involved in Ionomycin-Induced Neurotransmitter Release.PLOS ONE,9(4).
MLA	Zhang, Zhao,et al."Tyrosine 402 Phosphorylation of Pyk2 Is Involved in Ionomycin-Induced Neurotransmitter Release".PLOS ONE 9.4(2014).