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Activation of Phosphatidylinositol 3-Kinase in Cells Expressing abl Oncogene Variants

Varticovski, Lyuba and Daley, George Q. and Jackson, Peter and Baltimore, David and Cantley, Lewis C. (1991) Activation of Phosphatidylinositol 3-Kinase in Cells Expressing abl Oncogene Variants. Molecular and Cellular Biology, 11 (2). pp. 1107-1113. ISSN 0270-7306. http://resolver.caltech.edu/CaltechAUTHORS:20120420-071528647

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Abstract

A phosphoinositide kinase specific for the D-3 position of the inositol ring, phosphatidylinositol (PI) 3-kinase, associates with activated receptors for platelet-derived growth factor, insulin, and colony-stimulating factor 1, with products of the oncogenes src, fms, yes, crk, and with polyomavirus middle T antigen. Efficient fibroblast transformation by proteins of the abl and src oncogene families requires activation of their protein-tyrosine kinase activity and membrane association via an amino-terminal myristoylation. We have demonstrated that the PI 3-kinase directly associates with autophosphorylated, activated protein-tyrosine kinase variants of the abl protein. In vivo, this association leads to accumulation of the highly phosphorylated products of PI 3-kinase, PI-3,4-bisphosphate and PI-3,4,5-trisphosphate, only in myristoylated, transforming abl protein variants. Myristoylation thus appears to be required to recruit PI 3-kinase activity to the plasma membrane for in vivo activation and correlates with the mitogenicity of the abl protein variants.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1128/​MCB.11.2.1107DOIUNSPECIFIED
http://mcb.asm.org/content/11/2/1107.abstractPublisherUNSPECIFIED
Additional Information:© 1991 American Society for Microbiology. Received 18 July 1990. Accepted 26 November 1990. This work was supported in part by a grant from the Whitaker Health Science Fund (L.V. and D.B.) and by Public Health Service grants CA 51462 (G.Q.D., P.J., and D.B.), GM 36624 (L.C.C.), GM 41890 (L.C.C.), and NCI CA 53094 (L.V.) from the National Institutes of Health. We thank Marilyn Keeler for assistance with the HPLC analysis. We also thank Irwin M. Arias and Leona L. Ling for review of the manuscript.
Funders:
Funding AgencyGrant Number
Whitaker Health Science FundUNSPECIFIED
Public Health ServiceCA 51462
Public Health ServiceGM 36624
Public Health ServiceGM 41890
NIH NCI CA 53094
Record Number:CaltechAUTHORS:20120420-071528647
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20120420-071528647
Official Citation:Activation of phosphatidylinositol 3-kinase in cells expressing abl oncogene variants. L Varticovski, G Q Daley, P Jackson, D Baltimore, and L C Cantley Mol. Cell. Biol. February 1991 11:1107-1113; doi:10.1128/MCB.11.2.1107
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:30211
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:20 Apr 2012 14:51
Last Modified:20 Apr 2012 14:51

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