RGD Reference Report - p21-activated kinases regulate actin remodeling in glomerular podocytes. - Rat Genome Database

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p21-activated kinases regulate actin remodeling in glomerular podocytes.

Authors: Zhu, J  Attias, O  Aoudjit, L  Jiang, R  Kawachi, H  Takano, T 
Citation: Zhu J, etal., Am J Physiol Renal Physiol. 2010 Apr;298(4):F951-61. doi: 10.1152/ajprenal.00536.2009. Epub 2010 Jan 13.
RGD ID: 9835041
Pubmed: PMID:20071462   (View Abstract at PubMed)
DOI: DOI:10.1152/ajprenal.00536.2009   (Journal Full-text)

The tyrosine phosphorylation of nephrin is reported to regulate podocyte morphology via the Nck adaptor proteins. The Pak family of kinases are regulators of the actin cytoskeleton and are recruited to the plasma membrane via Nck. Here, we investigated the role of Pak in podocyte morphology. Pak1/2 were expressed in cultured podocytes. In mouse podocytes, Pak2 was predominantly phosphorylated, concentrated at the tips of the cellular processes, and its expression and/or phosphorylation were further increased when differentiated. Overexpression of rat nephrin in podocytes increased Pak1/2 phosphorylation, which was abolished when the Nck binding sites were mutated. Furthermore, dominant-negative Nck constructs blocked the Pak1 phosphorylation induced by antibody-mediated cross linking of nephrin. Transient transfection of constitutively kinase-active Pak1 into differentiated mouse podocytes decreased stress fibers, increased cortical F-actin, and extended the cellular processes, whereas kinase-dead mutant, kinase inhibitory construct, and Pak2 knockdown by shRNA had the opposite effect. In a rat model of puromycin aminonucleoside nephrosis, Pak1/2 phosphorylation was decreased in glomeruli, concomitantly with a decrease of nephrin tyrosine phosphorylation. These results suggest that Pak contributes to remodeling of the actin cytoskeleton in podocytes. Disturbed nephrin-Nck-Pak interaction may contribute to abnormal morphology of podocytes and proteinuria.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PAK2HumanPuromycin Aminonucleoside Nephrosis  ISOPak2 (Rattus norvegicus) RGD 
Pak2RatPuromycin Aminonucleoside Nephrosis  IEP  RGD 
Pak2MousePuromycin Aminonucleoside Nephrosis  ISOPak2 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Pak2  (p21 (RAC1) activated kinase 2)

Genes (Mus musculus)
Pak2  (p21 (RAC1) activated kinase 2)

Genes (Homo sapiens)
PAK2  (p21 (RAC1) activated kinase 2)


Additional Information