The phosphatidylinositol 3-kinase alpha is required for DNA synthesis induced by some, but not all, growth factors.
The phosphatidylinositol 3-kinase (PI 3-K) becomes activated when quiescent cells are stimulated with a variety of growth factors. We have microinjected antibodies specific for the p110 alpha subunit of the PI 3-K into quiescent fibroblasts and tested their effect on the ability of growth factors to stimulate exit from quiescence and entry into S phase. The antibodies inhibited platelet-derived growth factor-induced DNA synthesis, a result in keeping with previous studies using mutant platelet-derived growth factor receptors. Interestingly, functional PI 3-K was required for the first 6 hr of G1--i.e., until approximately 4 hr before the point at which the cells were committed to make DNA. A second tyrosine kinase receptor, the epidermal growth factor receptor, also required the PI 3-K for efficient signaling. However, colony-stimulating factor 1 (whose receptor is highly related to the platelet-derived growth factor receptor) could induce DNA synthesis in the absence of active PI 3-K, as could two growth factors (bombesin and lysophosphatidic acid) whose receptors are functionally coupled to G proteins. These data, therefore, demonstrate that some, but not all, growth factors require functional PI 3-K.
Roche
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Differentiation Programme, European Molecular Biology Laboratory, Heidelberg, Germany.
Koegl
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Courtneidge
S A
SA
D016475:3T3 Cells; D000818:Animals; D001839:Bombesin / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066298:In Vitro Techniques; D008246:Lysophospholipids / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D015398:Signal Transduction
D008246:Lysophospholipids; D010982:Platelet-Derived Growth Factor; D004815:Epidermal Growth Factor; D016173:Macrophage Colony-Stimulating Factor; D004247:DNA; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D001839:Bombesin