RGD Reference Report - Extracellular signal-regulated kinase activation during renal ischemia/reperfusion mediates focal adhesion dissolution and renal injury. - Rat Genome Database

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Extracellular signal-regulated kinase activation during renal ischemia/reperfusion mediates focal adhesion dissolution and renal injury.

Authors: Alderliesten, M  De Graauw, M  Oldenampsen, J  Qin, Y  Pont, C  Van Buren, L  Van de Water, B 
Citation: Alderliesten M, etal., Am J Pathol. 2007 Aug;171(2):452-62. Epub 2007 Jul 9.
RGD ID: 2292577
Pubmed: PMID:17620366   (View Abstract at PubMed)
PMCID: PMC1934533   (View Article at PubMed Central)
DOI: DOI:10.2353/ajpath.2007.060805   (Journal Full-text)

Acute renal failure due to ischemia/reperfusion involves disruption of integrin-mediated cellular adhesion and activation of the extracellular signal-regulated kinase (ERK) pathway. The dynamics of focal adhesion organization and phosphorylation during ischemia/reperfusion in relation to ERK activation are unknown. In control kidneys, protein tyrosine-rich focal adhesions, containing focal adhesion kinase, paxillin, and talin, were present at the basolateral membrane of tubular cells and colocalized with short F-actin stress fibers. Unilateral renal ischemia/reperfusion caused a reversible protein dephosphorylation and loss of focal adhesions. The focal adhesion protein phosphorylation rebounded in a biphasic manner, in association with increased focal adhesion kinase, Src, and paxillin tyrosine phosphorylation. Preceding phosphorylation of these focal adhesion proteins, reperfusion caused increased phosphorylation of ERK. The specific mitogen-activated protein kinase kinase 1/2 inhibitor U0126 prevented ERK activation and attenuated focal adhesion kinase, paxillin, and Src phosphorylation, focal adhesion restructuring, and ischemia/reperfusion-induced renal injury. We propose a model whereby ERK activation enhanced protein tyrosine phosphorylation during ischemia/reperfusion, thereby driving the dynamic dissolution and restructuring of focal adhesions and F-actin cytoskeleton during reperfusion and renal injury.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ischemia  ISOPtk2 (Rattus norvegicus)2292577; 2292577protein:decreased tyrosine phosphorylation:kidneyRGD 
ischemia  IEP 2292577protein:decreased tyrosine phosphorylation:kidneyRGD 
Reperfusion Injury  ISOPtk2 (Rattus norvegicus)2292577; 2292577protein:increased tyrosine phosphorylation:kidneyRGD 
Reperfusion Injury  IEP 2292577protein:increased tyrosine phosphorylation:kidneyRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
basolateral plasma membrane  IDA 2292577 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptk2  (protein tyrosine kinase 2)

Genes (Mus musculus)
Ptk2  (PTK2 protein tyrosine kinase 2)

Genes (Homo sapiens)
PTK2  (protein tyrosine kinase 2)


Additional Information