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

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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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to hydrogen peroxide  IEP 39131290 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
plasma membrane raft  IDA 39131290MMO:0000679RGD 

Objects Annotated

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


Additional Information