التفاصيل البيبلوغرافية
| العنوان: |
p21-Activated kinases regulate actin remodeling in glomerular podocytes. |
| المؤلفون: |
Jianxin Zhu1, Attias, Ortal1, Aoudjit, Lamine1, Ruihua Jiang1, Kawachi, Hiroshi2, Takano, Tomoko1 tomoko.takano@mcgill.ca |
| المصدر: |
American Journal of Physiology: Renal Physiology. Apr2010, Vol. 298, pF951-F961. 12p. |
| مصطلحات موضوعية: |
*KIDNEY glomerulus, *PROTEIN kinases, *CELL morphology, *ACTIN, *CYTOSKELETON, *PHOSPHORYLATION, *PUROMYCIN, *TYROSINE |
| مستخلص: |
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. Pakl/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 Pakl/2 phosphorylation, which was abolished when the Nck binding sites were mutated. Furthermore, dominant-negative Nck constructs blocked the Paki phosphorylation induced by antibody-mediated cross linking of nephrin. Transient transfection of constitutively kinase-active PakI 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 nephro- sis, Pakl/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. [ABSTRACT FROM AUTHOR] |
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