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Phee H , Au-Yeung BB , Pryshchep O , O'Hagan KL , Fairbairn SG , Radu M , Kosoff R , Mollenauer M , Cheng D , Chernoff J , Weiss A
Pak2 is required for actin cytoskeleton remodeling, TCR signaling, and normal thymocyte development and maturation
Elife. 2014 ;3 :e02270
AbstractThe molecular mechanisms that govern thymocyte development and maturation are incompletely understood. The P21-activated kinase 2 (Pak2) is an effector for the Rho family GTPases Rac and Cdc42 that regulate actin cytoskeletal remodeling, but its role in the immune system remains poorly understood. In this study, we show that T-cell specific deletion of Pak2 gene in mice resulted in severe T cell lymphopenia accompanied by marked defects in development, maturation, and egress of thymocytes. Pak2 was required for pre-TCR beta-selection and positive selection. Surprisingly, Pak2 deficiency in CD4 single positive thymocytes prevented functional maturation and reduced expression of S1P1 and KLF2. Mechanistically, Pak2 is required for actin cytoskeletal remodeling triggered by TCR. Failure to induce proper actin cytoskeletal remodeling impaired PLCgamma1 and Erk1/2 signaling in the absence of Pak2, uncovering the critical function of Pak2 as an essential regulator that governs the actin cytoskeleton-dependent signaling to ensure normal thymocyte development and maturation.DOI: http://dx.doi.org/10.7554/eLife.02270.001.
Notes2050-084x Phee, Hyewon Au-Yeung, Byron B Pryshchep, Olga O'Hagan, Kyle Leonard Fairbairn, Stephanie Grace Radu, Maria Kosoff, Rachelle Mollenauer, Marianne Cheng, Debra Chernoff, Jonathan Weiss, Arthur Journal Article United States Elife. 2014 May 13;3:e02270. doi: 10.7554/eLife.02270.