Src kinase up-regulates the ERK cascade through inactivation of protein phosphatase 2A following cerebral ischemia
<p>Abstract</p> <p>Background</p> <p>The regulation of protein phosphorylation requires a balance in the activity of protein kinases and protein phosphatases. Our previous data indicates that Src can increase ERK activity through Raf kinase in response to ischemic stimu...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-07-01
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| Series: | BMC Neuroscience |
| Online Access: | http://www.biomedcentral.com/1471-2202/10/74 |
| _version_ | 1818389872119906304 |
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| author | Xu Jiali Wu Xiangyang Hu Xiaohan Zhou Jin Han Xiao Guo Jun |
| author_facet | Xu Jiali Wu Xiangyang Hu Xiaohan Zhou Jin Han Xiao Guo Jun |
| author_sort | Xu Jiali |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The regulation of protein phosphorylation requires a balance in the activity of protein kinases and protein phosphatases. Our previous data indicates that Src can increase ERK activity through Raf kinase in response to ischemic stimuli. This study examined the molecular mechanisms by which Src activates ERK cascade through protein phosphatases following cerebral ischemia.</p> <p>Results</p> <p>Ischemia-induced Src activation is followed by phosphorylation of PP2A at Tyr307 leading to its inhibition in the rat hippocampus. SU6656, a Src inhibitor, up-regulates PP2A activity, resulting in a significant decreased activity in ERK and its targets, CREB and ERα. In addition, the PP2A inhibitor, cantharidin, led to an up-regulation of ERK activity and was able to counteract Src inhibition during ischemia.</p> <p>Conclusion</p> <p>Src induces up-regulation of ERK activity and its target transcription factors, CREB and ERα, through attenuation of PP2A activity. Therefore, activation of ERK is the result of a crosstalk between two pathways, Raf-dependent positive regulators and PP2A-dependent negative regulators.</p> |
| first_indexed | 2024-12-14T04:48:38Z |
| format | Article |
| id | doaj.art-faab1fad2161457c854dabe16e0f7162 |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-12-14T04:48:38Z |
| publishDate | 2009-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-faab1fad2161457c854dabe16e0f71622022-12-21T23:16:37ZengBMCBMC Neuroscience1471-22022009-07-011017410.1186/1471-2202-10-74Src kinase up-regulates the ERK cascade through inactivation of protein phosphatase 2A following cerebral ischemiaXu JialiWu XiangyangHu XiaohanZhou JinHan XiaoGuo Jun<p>Abstract</p> <p>Background</p> <p>The regulation of protein phosphorylation requires a balance in the activity of protein kinases and protein phosphatases. Our previous data indicates that Src can increase ERK activity through Raf kinase in response to ischemic stimuli. This study examined the molecular mechanisms by which Src activates ERK cascade through protein phosphatases following cerebral ischemia.</p> <p>Results</p> <p>Ischemia-induced Src activation is followed by phosphorylation of PP2A at Tyr307 leading to its inhibition in the rat hippocampus. SU6656, a Src inhibitor, up-regulates PP2A activity, resulting in a significant decreased activity in ERK and its targets, CREB and ERα. In addition, the PP2A inhibitor, cantharidin, led to an up-regulation of ERK activity and was able to counteract Src inhibition during ischemia.</p> <p>Conclusion</p> <p>Src induces up-regulation of ERK activity and its target transcription factors, CREB and ERα, through attenuation of PP2A activity. Therefore, activation of ERK is the result of a crosstalk between two pathways, Raf-dependent positive regulators and PP2A-dependent negative regulators.</p>http://www.biomedcentral.com/1471-2202/10/74 |
| spellingShingle | Xu Jiali Wu Xiangyang Hu Xiaohan Zhou Jin Han Xiao Guo Jun Src kinase up-regulates the ERK cascade through inactivation of protein phosphatase 2A following cerebral ischemia BMC Neuroscience |
| title | Src kinase up-regulates the ERK cascade through inactivation of protein phosphatase 2A following cerebral ischemia |
| title_full | Src kinase up-regulates the ERK cascade through inactivation of protein phosphatase 2A following cerebral ischemia |
| title_fullStr | Src kinase up-regulates the ERK cascade through inactivation of protein phosphatase 2A following cerebral ischemia |
| title_full_unstemmed | Src kinase up-regulates the ERK cascade through inactivation of protein phosphatase 2A following cerebral ischemia |
| title_short | Src kinase up-regulates the ERK cascade through inactivation of protein phosphatase 2A following cerebral ischemia |
| title_sort | src kinase up regulates the erk cascade through inactivation of protein phosphatase 2a following cerebral ischemia |
| url | http://www.biomedcentral.com/1471-2202/10/74 |
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