Effect of transformation by Rous sarcoma virus on the character and distribution of actin in Rat-1 fibroblasts: A biochemical and microscopical study

Holme, T C; Kellie, Stuart; Wyke, John A.; Crawford, N.

doi:10.1038/bjc.1986.74

Cited by 30 publications

(19 citation statements)

References 33 publications

(29 reference statements)

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“…The reorganization of actin filaments into podosomes upon transformation correlates with an increase in the amount of actin partitioning in the Triton-resistant fraction (34). It is clear, however, that the increased presence of actin in this fraction alone cannot account for the redistribution of cortactin.…”

Section: Discussionmentioning

confidence: 91%

p80/85 Cortactin Associates with the Src SH2 Domain and Colocalizes with v-Src in Transformed Cells

Okamura

Resh

1995

Journal of Biological Chemistry

111

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Expression of oncogenic variants of pp60src leads to dramatic changes in cytoskeletal organization characteristic of transformation. Activated Src associates with the cytoskeletal matrix, resulting in tyrosine phosphorylation of specific cytoskeletal substrates. We have previously shown that stable association of Src with the cytoskeletal matrix is mediated by the Src SH2 domain in a phosphotyrosine-dependent interaction. In this report, we demonstrate that one of the cytoskeletal binding partners of Src is p80/85 cortactin. The association was observed in lysates of transformed cells but was not seen in normal fibroblasts. The interaction could be reconstituted in vitro using transformed cell extracts and a glutathione S-transferase (GST) fusion protein containing the Src SH2 domain but not with GST-Src SH3 or with GST-Src SH2 containing a point mutation in the FLVRES sequence. Confocal microscopy revealed that cortactin redistributed and colocalized with v-Src and a Src SH3 deletion mutant in transformed cells. However, in cells expressing a Src SH2 deletion mutant, the redistribution of cortactin and colocalization with Src did not occur. Furthermore, biochemical fractionation of transformed cells indicated that a significant increase in cortactin distribution to the cytoskeletal fraction occurred, which correlated with a shift in the tyrosinephosphorylated form of the protein. Cortactin fractionated from cells expressing kinase-defective or myristylation-defective Src mutants did not exhibit this shift. These data suggest a molecular mechanism by which tyrosine phosphorylation of cortactin and association with the Src SH2 domain influence the cytoskeletal reorganization induced in Src-transformed cells.

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Section: Discussionmentioning

confidence: 91%

p80/85 Cortactin Associates with the Src SH2 Domain and Colocalizes with v-Src in Transformed Cells

Okamura

Resh

1995

Journal of Biological Chemistry

111

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“…The polymerization state and stability of the actin cytoskeleton has been shown to vary with the state of cell differentiation and with cellular transformation in non-lymphoid systems [Nagata et al, 1980;Meyer and Howard, 1983;Antecol et al, 1986;Holme et al, 1986;Katsantonis et al, 1994;Hemstreet et al, 1996;Stournaras et al, 1996;Rao et al, 1997]. Additional studies support a role for the actin cytoskeleton in the coordinated control of cell cycle events [Vojtek et al, 1991;Gomez et al, 1997] and demonstrate that actin-related events such as adhesion, receptor clustering, or receptor internalization can affect mitogenic or survival signals [Rao, 1982;Brock and Chrest, 1993;Rozdzial et al, 1995;Valitutti et al, 1995].…”

Section: Discussionmentioning

confidence: 98%

Inhibition of actin polymerization enhances commitment to and execution of apoptosis induced by withdrawal of trophic support

Morley

Sun

Bierer

2003

J of Cellular Biochemistry

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We have previously shown, using jasplakinolide, that stabilization of the actin cytoskeleton enhanced apoptosis induced upon cytokine withdrawal (Posey and Bierer [1999] J. Biol. Chem. 274:4259-4265). It remained possible, however, that a disruption in the regulation of actin dynamics, and not simply F-actin stabilization, was required to affect the transduction of an apoptotic signal. We have now tested the effects of cytochalasin D, a well-characterized agent that promoted actin depolymerization. Actin depolymerization did not affect CD95 (Fas)-induced death of Jurkat T cells in the time course studied but did enhance the commitment to cytokine withdrawal-induced apoptosis of factor-dependent cell lines. The induction of cell death was not the result of direct cytoskeletal collapse, since treatment of the cells with cytochalasin D in the presence of IL-2 did not promote death. As with jasplakinolide, the enhancement of commitment to apoptosis could be delayed by overexpression of the anti-apoptotic protein Bcl-x(L), but, unlike jasplakinolide, cytochalasin D modestly affected the "execution" stage of apoptosis as well. Taken together, these results suggest that changes in actin dynamics, i.e., the rate of actin polymerization and depolymerization, modulate the transduction of the apoptotic signal committing lymphocytes, withdrawn from required growth factors, to the death pathway.

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“…One of these systems, microfilament actin, plays a critical role in maintenance of cellular morphology, growth and differentiation, and motility of cells [2,3]. Alterations in cytoskeletal organization, particularly of actin filaments, have been implicated in tumorigenesis [4,5].…”

Section: Introductionmentioning

confidence: 99%

“…The change of cellular morphology in transformed and malignant cells is also linked to decreased expression of actin-binding proteins (ABP) [4].…”

Section: Introductionmentioning

confidence: 99%

Downregulated gelsolin expression in hyperplastic and neoplastic lesions of the prostate

et al. 1999

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Effect of transformation by Rous sarcoma virus on the character and distribution of actin in Rat-1 fibroblasts: A biochemical and microscopical study

Cited by 30 publications

References 33 publications

p80/85 Cortactin Associates with the Src SH2 Domain and Colocalizes with v-Src in Transformed Cells

p80/85 Cortactin Associates with the Src SH2 Domain and Colocalizes with v-Src in Transformed Cells

Inhibition of actin polymerization enhances commitment to and execution of apoptosis induced by withdrawal of trophic support

Downregulated gelsolin expression in hyperplastic and neoplastic lesions of the prostate

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