Tyrosine 402 phosphorylation of Pyk2 is involved in ionomycin-induced neurotransmitter release.
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3981813?pdf=render |
| _version_ | 1818301898479894528 |
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| author | Zhao Zhang Yun Zhang Zheng Mou Shifeng Chu Xiaoyu Chen Wenbin He Xiaofeng Guo Yuhe Yuan Masami Takahashi Naihong Chen |
| author_facet | Zhao Zhang Yun Zhang Zheng Mou Shifeng Chu Xiaoyu Chen Wenbin He Xiaofeng Guo Yuhe Yuan Masami Takahashi Naihong Chen |
| author_sort | Zhao Zhang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T05:30:20Z |
| format | Article |
| id | doaj.art-892dfd5c91eb4e85b305aca101c7f935 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T05:30:20Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-892dfd5c91eb4e85b305aca101c7f9352022-12-21T23:58:05ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0194e9457410.1371/journal.pone.0094574Tyrosine 402 phosphorylation of Pyk2 is involved in ionomycin-induced neurotransmitter release.Zhao ZhangYun ZhangZheng MouShifeng ChuXiaoyu ChenWenbin HeXiaofeng GuoYuhe YuanMasami TakahashiNaihong ChenProtein 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.http://europepmc.org/articles/PMC3981813?pdf=render |
| spellingShingle | Zhao Zhang Yun Zhang Zheng Mou Shifeng Chu Xiaoyu Chen Wenbin He Xiaofeng Guo Yuhe Yuan Masami Takahashi Naihong Chen Tyrosine 402 phosphorylation of Pyk2 is involved in ionomycin-induced neurotransmitter release. PLoS ONE |
| title | Tyrosine 402 phosphorylation of Pyk2 is involved in ionomycin-induced neurotransmitter release. |
| title_full | Tyrosine 402 phosphorylation of Pyk2 is involved in ionomycin-induced neurotransmitter release. |
| title_fullStr | Tyrosine 402 phosphorylation of Pyk2 is involved in ionomycin-induced neurotransmitter release. |
| title_full_unstemmed | Tyrosine 402 phosphorylation of Pyk2 is involved in ionomycin-induced neurotransmitter release. |
| title_short | Tyrosine 402 phosphorylation of Pyk2 is involved in ionomycin-induced neurotransmitter release. |
| title_sort | tyrosine 402 phosphorylation of pyk2 is involved in ionomycin induced neurotransmitter release |
| url | http://europepmc.org/articles/PMC3981813?pdf=render |
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