Changes in cytoskeletal organization in polyoma middle T antigen-transformed fibroblasts: involvement of protein phosphatase 2A and src tyrosine kinases |
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Authors: | da Costa S R Wang Y Vilalta P M Schönthal A H Hamm-Alvarez S F |
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Affiliation: | Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90033, USA. |
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Abstract: | The major transforming activity of polyomavirus, middle T antigen, targets several cellular regulatory effectors including protein phosphatase 2A and src tyrosine kinases. Although transformed cells exhibit profound morphological changes, little is known about how middle T antigen-induced changes in the cellular regulatory environment specifically affect the cytoskeleton. We have investigated these changes in 10T(1/2) mouse fibroblasts transformed with polyoma middle T antigen. Immunofluorescence microscopy revealed that expression of middle T antigen (Pym T cells) depleted the stable (acetylated) microtubule array and increased the sensitivity of dynamic (tyrosinated) microtubules to nocodazole-induced disassembly. These effects were associated with a modest but statistically significant (P=0.05) increase in recovery of protein phosphatase 2A activity with microtubules. Middle T antigen expression also depleted the normal cellular complement of actin stress fibers and focal adhesions, in parallel with changes in the distribution of src tyrosine kinases. Herbimycin A promoted recovery of paxillin and phosphotyrosine into nascent focal adhesion sites, in addition to restoring normal src tyrosine kinase distribution. However, herbimycin A did not restore actin stress fibers or parental-type microtubules to Pym T cells. We suggest that regulation of the microtubule array by middle T antigen may occur through direct effects including redistribution of protein phosphatase 2A as well as indirect effects such as altered interactions with actin-based stress fibers. |
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