A mutant form of the rho protein can restore stress fibers and adhesion plaques in v-src transformed fibroblasts

Mayer, Thomas; Meyer, Markus; Janning, Annette; Schiedel, Anke C.; Barnekow, Angelika

doi:10.1038/sj.onc.1202537

Cited by 37 publications

(31 citation statements)

References 52 publications

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“…Consistent with our findings, v-Src inhibited cofilin phosphorylation and the mechanism involved a MEK-dependent and PI3 kinase-independent pathway (Pawlak and Helfman, 2002). Rho mutants restore stress fiber formation in v-Src-transformed cells (Mayer et al, 1999), consistent with a model in which Rho proteins serve as downstream targets of v-Src. In our studies, c-Jun reintroduction into c-jun Ϫ/Ϫ cells inhibited Rho kinase activity and induced cellular migration.…”

Section: Discussionsupporting

confidence: 78%

Disruption of c-Jun Reduces Cellular Migration and Invasion through Inhibition of c-Src and Hyperactivation of ROCK II Kinase

Jiao¹,

Katiyar²,

Liu³

et al. 2008

MBoC

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The spread of metastatic tumors to different organs is associated with poor prognosis. The metastatic process requires migration and cellular invasion. The protooncogene c-jun encodes the founding member of the activator protein-1 family and is required for cellular proliferation and DNA synthesis in response to oncogenic signals and plays an essential role in chemical carcinogenesis. The role of c-Jun in cellular invasion remains to be defined. Genetic deletion of c-Jun in transgenic mice is embryonic lethal; therefore, transgenic mice encoding a c-Jun gene flanked by LoxP sites (c-junf/f) were used. c-jun gene deletion reduced c-Src expression, hyperactivated ROCK II signaling, and reduced cellular polarity, migration, and invasiveness. c-Jun increased c-Src mRNA abundance and c-Src promoter activity involving an AP-1 site in the c-Src promoter. Transduction of c-jun−/− cells with either c-Jun or c-Src retroviral expression systems restored the defective cellular migration of c-jun−/− cells. As c-Src is a critical component of pathways regulating proliferation, survival, and metastasis, the induction of c-Src abundance, by c-Jun, provides a novel mechanism of cooperative signaling in cellular invasion.

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Section: Discussionsupporting

confidence: 78%

Disruption of c-Jun Reduces Cellular Migration and Invasion through Inhibition of c-Src and Hyperactivation of ROCK II Kinase

Jiao¹,

Katiyar²,

Liu³

et al. 2008

MBoC

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“…Transfection efficiency was about 50%. Reprobing the blot with an anti-EE epitope antibody confirmed that the EE-tagged RhoA proteins migrate with a higher apparent molecular weight than endogenous RhoA (not shown); the 63L and V14 point mutations are known to alter the migration of RhoA differently (73). The data in a and c are the means Ϯ S.D.…”

Section: Rho Activation In Nih 3t3 Ltr-h-ras(a) Cells and Nih 3t3 Celmentioning

confidence: 97%

Oncogenic Ras Leads to Rho Activation by Activating the Mitogen-activated Protein Kinase Pathway and Decreasing Rho-GTPase-activating Protein Activity

Chen¹,

Zhuang²,

Nguyen

et al. 2003

Journal of Biological Chemistry

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Transformation by oncogenic Ras requires signaling through Rho family proteins including RhoA, but the mechanism(s) whereby oncogenic Ras regulates the activity of RhoA is (are) unknown. We examined the effect of Ras on RhoA activity in NIH 3T3 cells either stably transfected with H-Ras(V12) under control of an inducible promoter or transiently expressing the activated H-Ras. Using a novel method to quantitate enzymatically the GTP bound to Rho, we found that expression of the oncogenic Ras increased Rho activity ϳ2-fold. Increased Rho activity was associated with increased plasma membrane binding of RhoA and decreased activity of the Rho/Ras-regulated p21 WAF1/CIP1 promoter. RhoA activation by oncogenic Ras could be explained by a decrease in cytosolic p190 Rho-GAP activity and translocation of p190 Rho-GAP from the cytosol to a detergent-insoluble cytoskeletal fraction. Pharmacologic inhibition of the Ras/Raf/MEK/ERK pathway prevented Ras-induced activation of RhoA and translocation of p190 Rho-GAP; expression of constitutively active Raf-1 kinase or MEK was sufficient to induce p190 Rho-GAP translocation. We conclude that in NIH 3T3 cells oncogenic Ras activates RhoA through the Raf/MEK/ERK pathway by decreasing the cytosolic activity and changing the subcellular localization of p190 Rho-GAP.

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“…Activated Rho can restore actin ®lament organization in Src-transformed cells (Mayer et al, 1999), and cSrc activation requires the inactivation of Rho, by enhancing GTPase activity, to induce actin ®lament dissolution (Fincham et al, 1999). GFP-AFAP-110 Dlzip was co-expressed in C3H10T1/2 cells with dominant positive Rho (RhoA V14 ) to determine if GFP-AFAP-110 Dlzip may exert its a ects on actin ®laments in a Rho-dependent fashion.…”

Section: Afap-110 Dlzip Alters Actin Filaments In a Rho-dependent Fasmentioning

confidence: 99%

The intrinsic ability of AFAP-110 to alter actin filament integrity is linked with its ability to also activate cellular tyrosine kinases

et al. 2001

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The actin ®lament-associated protein of 110 kDa (AFAP-110) is a Src binding partner that represents a potential modulator of actin ®lament integrity in response to cellular signals. Previous reports have demonstrated that AFAP-110 is capable of directly binding and altering actin ®laments. Deletion of the leucine zipper motif of AFAP-110 (AFAP-110 Dlzip ) has been shown to induce a phenotype which resembles Srctransformed cells, by repositioning actin ®laments into rosettes. This deletion also mimics a conformational change in AFAP-110 that is detected in Src-transformed cells. The results presented here indicate that unlike AFAP-110, AFAP-110 Dlzip is capable of activating cellular tyrosine kinases, including Src family members, and that AFAP-110 Dlzip itself is hyperphosphorylated. The newly tyrosine phosphorylated proteins and activated Src-family members appear to be associated with actinrich lamellipodia. A point mutation that alters the SH3-binding motif of AFAP-110 Dlzip prevents it from activating tyrosine kinases and altering actin ®lament integrity. In addition, a deletion within a pleckstrin homology (PH) domain of AFAP-110 Dlzip will also revert its e ects upon actin ®laments. Lastly, dominant-positive RhoA V14 will block the ability of AFAP-110 Dlzip from inducing actin ®lament rosettes, but does not inhibit Src activation. Thus, conformational changes in AFAP-110 enable it to activate cellular kinases in a mechanism requiring SH3 and/or PH domain interactions. We hypothesize that cellular signals which alter AFAP-110 conformation, enable it to activate cellular kinases such as cSrc, which then direct changes in actin ®lament integrity in a Rho-dependent fashion. Oncogene (2001) 20, 6607 ± 6616.

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A mutant form of the rho protein can restore stress fibers and adhesion plaques in v-src transformed fibroblasts

Cited by 37 publications

References 52 publications

Disruption of c-Jun Reduces Cellular Migration and Invasion through Inhibition of c-Src and Hyperactivation of ROCK II Kinase

Disruption of c-Jun Reduces Cellular Migration and Invasion through Inhibition of c-Src and Hyperactivation of ROCK II Kinase

Oncogenic Ras Leads to Rho Activation by Activating the Mitogen-activated Protein Kinase Pathway and Decreasing Rho-GTPase-activating Protein Activity

The intrinsic ability of AFAP-110 to alter actin filament integrity is linked with its ability to also activate cellular tyrosine kinases

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