Email updates

Keep up to date with the latest news and content from BMC Neuroscience and BioMed Central.

Open Access Highly Accessed Research article

Src kinase up-regulates the ERK cascade through inactivation of protein phosphatase 2A following cerebral ischemia

Xiaohan Hu12, Xiangyang Wu123, Jiali Xu24, Jin Zhou23, Xiao Han12 and Jun Guo124*

Author Affiliations

1 Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing 210029, PR China

2 Department of Biochemistry, Nanjing Medical University, Nanjing 210029, PR China

3 Department of General Surgery, The Nanjing First Hospital Affiliated to Nanjing Medical University, Nanjing 210006, PR China

4 Laboratory Center for Basic Medical Sciences, Nanjing medical university Nanjing, 210029, PR China

For all author emails, please log on.

BMC Neuroscience 2009, 10:74  doi:10.1186/1471-2202-10-74

Published: 14 July 2009

Abstract

Background

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.

Results

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.

Conclusion

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.