Role of phosphoinositide 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras

Rodriguez-Viciana, P., Warne, P. H., Khwaja, A., Marte, B. M., Pappin, D., Das, P., Waterfield, M. D., Ridley, A., Downward, J. (May 1997) Role of phosphoinositide 3-OH kinase in cell transformation and control of the actin cytoskeleton by Ras. Cell, 89 (3). pp. 457-67. ISSN 0092-8674 (Print)0092-8674 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/9150145
DOI: 10.1016/S0092-8674(00)80226-3

Abstract

The pathways by which mammalian Ras proteins induce cortical actin rearrangement and cause cellular transformation are investigated using partial loss of function mutants of Ras and activated and inhibitory forms of various postulated target enzymes for Ras. Efficient transformation by Ras requires activation of other direct effectors in addition to the MAP kinase kinase kinase Raf and is inhibited by inactivation of the PI 3-kinase pathway. Actin rearrangement correlates with the ability of Ras mutants to activate PI 3-kinase. Inhibition of PI 3-kinase activity blocks Ras induction of membrane ruffling, while activated PI 3-kinase is sufficient to induce membrane ruffling, acting through Rac. The ability of activated Ras to stimulate PI 3-kinase in addition to Raf is therefore important in Ras transformation of mammalian cells and essential in Ras-induced cytoskeletal reorganization.

Item Type: Paper
Additional Information: Rodriguez-Viciana, P Warne, P H Khwaja, A Marte, B M Pappin, D Das, P Waterfield, M D Ridley, A Downward, J United states Cell Cell. 1997 May 2;89(3):457-67.
Uncontrolled Keywords: 3T3 Cells/chemistry/cytology/enzymology Actins/ metabolism Animals Aorta/cytology COS Cells/chemistry/cytology/enzymology Cell Membrane/physiology Cell Size/physiology Chromones/pharmacology Cytoskeleton/ metabolism Endothelium, Vascular/cytology Enzyme Inhibitors/pharmacology Mice Morpholines/pharmacology Mutation/physiology Naphthalenes/pharmacology Phosphatidylinositol 3-Kinases Phosphatidylinositol Phosphates/metabolism Phosphotransferases (Alcohol Group Acceptor)/ physiology Platelet-Derived Growth Factor/metabolism Protein Kinase C/antagonists & inhibitors Swine Transformation, Genetic/drug effects/ physiology ras Proteins/genetics/ metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > RAS
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > actin
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > phosphoinositide 3-kinase
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > Protein kinase C
CSHL Authors:
Communities: CSHL labs > Pappin lab
Depositing User: Kathleen Darby
Date: 2 May 1997
Date Deposited: 08 May 2014 15:13
Last Modified: 08 May 2014 15:13
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29986

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