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Research Article

Activation of phosphatidylinositol 3-kinase in cells expressing abl oncogene variants.

L Varticovski, G Q Daley, P Jackson, D Baltimore, L C Cantley
L Varticovski
Department of Biomedical Research, St. Elizabeth's Hospital, Boston, Massachusetts 02135.
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G Q Daley
Department of Biomedical Research, St. Elizabeth's Hospital, Boston, Massachusetts 02135.
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P Jackson
Department of Biomedical Research, St. Elizabeth's Hospital, Boston, Massachusetts 02135.
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D Baltimore
Department of Biomedical Research, St. Elizabeth's Hospital, Boston, Massachusetts 02135.
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L C Cantley
Department of Biomedical Research, St. Elizabeth's Hospital, Boston, Massachusetts 02135.
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DOI: 10.1128/MCB.11.2.1107
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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.

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Activation of phosphatidylinositol 3-kinase in cells expressing abl oncogene variants.
L Varticovski, G Q Daley, P Jackson, D Baltimore, L C Cantley
Molecular and Cellular Biology Feb 1991, 11 (2) 1107-1113; DOI: 10.1128/MCB.11.2.1107

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Activation of phosphatidylinositol 3-kinase in cells expressing abl oncogene variants.
L Varticovski, G Q Daley, P Jackson, D Baltimore, L C Cantley
Molecular and Cellular Biology Feb 1991, 11 (2) 1107-1113; DOI: 10.1128/MCB.11.2.1107
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