RGD Reference Report - Repetitive peroxide exposure reveals pleiotropic mitogen-activated protein kinase signaling mechanisms. - Rat Genome Database

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Repetitive peroxide exposure reveals pleiotropic mitogen-activated protein kinase signaling mechanisms.

Authors: Chadwick, W  Park, SS  Zhou, Y  Wang, L  Brenneman, R  Martin, B  Maudsley, S  Maudsley, Stuart 
Citation: Chadwick W, etal., J Signal Transuct. 2011;2011. pii: 636951.
RGD ID: 5131481
Pubmed: PMID:21258655   (View Abstract at PubMed)
PMCID: PMC3023409   (View Article at PubMed Central)
DOI: DOI:10.1155/2011/636951   (Journal Full-text)

Oxidative stressors such as hydrogen peroxide control the activation of many interconnected signaling systems and are implicated in neurodegenerative disease etiology. Application of hydrogen peroxide to PC12 cells activated multiple tyrosine kinases (c-Src, epidermal growth factor receptor (EGFR) and Pyk2) and the serine-threonine kinase ERK1/2. Peroxide-induced ERK1/2 activation was sensitive to intracellular calcium chelation and EGFR and c-Src kinase inhibition. Acute application and removal of peroxide allowed ERK1/2 activity levels to rapidly subside to basal serum-deprived levels. Using this protocol we demonstrated that ERK1/2 activation tachyphylaxis developed upon repeated peroxide exposures. This tachyphylaxis was independent of c-Src/Pyk2 tyrosine phosphorylation but was associated with a progressive reduction of peroxide-induced EGFR tyrosine phosphorylation, EGFR interaction with growth factor receptor binding protein 2 and a redistribution of EGFR from the plasma membrane to the cytoplasm. Our data indicates that components of peroxide-induced ERK1/2 cascades are differentially affected by repeated exposures, indicating that oxidative signaling may be contextually variable.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
hydrogen peroxide metabolic process  IEP 5131481 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
epidermal growth factor receptor binding  IPIEgfr (Rattus norvegicus)5131481 RGD 
protein binding  IPIGrb2 (Rattus norvegicus)5131481 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Egfr  (epidermal growth factor receptor)
Grb2  (growth factor receptor bound protein 2)


Additional Information