Role of Phosphoinositide 3-OH Kinase in Cell Transformation and Control of the Actin Cytoskeleton by Ras

  title={Role of Phosphoinositide 3-OH Kinase in Cell Transformation and Control of the Actin Cytoskeleton by Ras},
  author={Pablo Rodriguez-Viciana and Patricia H. Warne and Asim Ijaz Khwaja and Barbara M. Marte and Darryl J. Pappin and Pamela Das and Michael D. Waterfield and Anne J. Ridley and Julian Downward},

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Transformation Potential of Ras Isoforms Correlates with Activation of Phosphatidylinositol 3-Kinase but Not ERK*
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Two further effector pathways for TC21 are identified, which contribute to TC21-stimulated transformation and inhibition of Ral signaling blocks DNA synthesis in human tumor cell lines containing activating mutations in TC21, demonstrating for the first time that this pathway is required for the proliferation of human tumor cells.
Protein Kinase B Activation and Lamellipodium Formation Are Independent Phosphoinositide 3-Kinase-Mediated Events Differentially Regulated by Endogenous Ras
It is concluded that, in vivo, p85 and Ras synergize to activate PI 3-kinase and that strong activation of only endogenous Ras exerts a small effect on PI 3 -kinase activity, sufficient for PKB activation but not lamellipodium formation.


Activation of phosphoinositide 3-kinase is required for PDGF-stimulated membrane ruffling
Activation of phosphoinositide 3‐kinase by interaction with Ras and by point mutation.
The data show that PI 3‐kinase is regulated by a number of mechanisms, and that Ras contributes to the activation of this lipid kinase synergistically with tyrosine kinases.
PDGF stimulates an increase in GTP–Rac via activation of phosphoinositide 3-kinase
Phosphatidylinositol-3-OH kinase direct target of Ras
In vivo, dominant negative Ras mutant N17 inhibits growth factor induced production of 3′ hosphorylated phosphoinositides in PC12 cells, and transfection of Ras, but not Raf, into COS cells results in a large elevation in the level of these lipids.
Stimulation of Membrane Ruffling and MAP Kinase Activation by Distinct Effectors of RAS
Results indicate that membrane ruffling and activation of MAP kinase represent distinct RAS effector pathways and that input from both pathways is required for the mitogenic activity of RAS.
Activation of extracellular signal‐regulated kinase, ERK2, by p21ras oncoprotein.
It is proposed that the kinases that are activated following the scrape loading of p21ras into quiescent cells are important components of the signal transduction pathway activated by p 21ras oncoprotein.
Activation of Rac1, RhoA, and mitogen-activated protein kinases is required for Ras transformation
Data support the possibility that oncogenic Ras activation of Rac1 and RhoA, coupled with activation of the Raf/MAPK pathway, is required to trigger the full morphogenic and mitogenic consequences of oncogen Ras transformation.
An essential role for Rac in Ras transformation
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A role for Rho in Ras transformation.
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