RGD Reference Report - Oxidative stress induces lipid-raft-mediated activation of Src homology 2 domain-containing protein-tyrosine phosphatase 2 in astrocytes.

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Oxidative stress induces lipid-raft-mediated activation of Src homology 2 domain-containing protein-tyrosine phosphatase 2 in astrocytes.
Authors:	Park, Soo Jung Kim, Hee Young Kim, Hyunmi Park, Sang Myun Joe, Eun-hye Jou, Ilo Choi, Youn-Hee
Citation:	Park SJ, etal., Free Radic Biol Med. 2009 Jun 15;46(12):1694-702. doi: 10.1016/j.freeradbiomed.2009.03.026. Epub 2009 Apr 5.
RGD ID:	39131290
Pubmed:	PMID:19348936 (View Abstract at PubMed)
DOI:	DOI:10.1016/j.freeradbiomed.2009.03.026 (Journal Full-text)
Several protein phosphatases are involved in neuroprotection in response to ischemic brain injury. Here, we report that reactive oxygen species (ROS)-mediated oxidative stress promotes phosphorylation of endogenous SHP-2 through lipid rafts in rat primary astrocytes. SHP-2 was transiently phosphorylated during hypoxia/reoxygenation, an effect abrogated by a ROS scavenger and an NADPH oxidase inhibitor. Additionally, exogenous treatment with hydrogen peroxide (H(2)O(2)) triggered SHP-2 phosphorylation in a time- and dose-dependent manner and led to its translocation into lipid rafts. H(2)O(2)-mediated SHP-2 phosphorylation and translocation were inhibited by filipin III and methyl-beta-cyclodextrin (MCD), lipid-raft-disrupting agents. In the presence of H(2)O(2), SHP-2 formed a complex with STAT-3 and reduced the steady-state STAT-3 phosphorylation level. Interestingly, the effect of H(2)O(2) on SHP-2 phosphorylation was cell-type specific. Remarkably, SHP-2 phosphorylation was induced strongly by H(2)O(2) in astrocytes, but barely detectable in microglia. Our results collectively indicate that SHP-2 is activated by ROS-mediated oxidative stress in astrocytes and functions as a component of the raft-mediated signaling pathway that acts through dephosphorylation and inactivation of other phosphotyrosine proteins, such as STAT-3.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Ptpn11	Rat	cellular response to hydrogen peroxide		IEP			RGD

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Ptpn11	Rat	plasma membrane raft		IDA		MMO:0000679	RGD

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Genes (Rattus norvegicus)

Ptpn11 (protein tyrosine phosphatase, non-receptor type 11)

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Oxidative stress induces lipid-raft-mediated activation of Src homology 2 domain-containing protein-tyrosine phosphatase 2 in astrocytes.