THE PHOSPHATIDYLINOSITOL 3-KINASE-ALPHA IS REQUIRED FOR DNA-SYNTHESISINDUCED BY SOME, BUT NOT ALL, GROWTH-FACTORS

The phosphatidylinositol 3-kinase (PI 3-K) becomes activated when quie scent cells are stimulated with a variety of growth factors. We have m icroinjected 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 p hase. 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 G(1)-i.e., until approximate t o 4 hr before the point at which the cells were committed to make DNA. A second tyrosine kinase receptor, the epidermal growth factor recept or, 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 abs ence of active PI 3-K, as could two growth factors (bombesin and lysop hosphatidic acid) whose receptors are functionally coupled to G protei ns. These data, therefore, demonstrate that some, but not all, growth factors require functional PI 3-K.