TY - JOUR
T1 - The phosphatidylinositol 3-kinase α is required for DNA synthesis induced by some, but not all, growth factors
AU - Roche, Serge
AU - Koegl, Manfred
AU - Courtneidge, Sara A.
PY - 1994/9/13
Y1 - 1994/9/13
N2 - 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 p110α 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 ≃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.
AB - 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 p110α 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 ≃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.
KW - microinjection
KW - protein-tyrosine kinases
KW - signal transduction
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U2 - 10.1073/pnas.91.19.9185
DO - 10.1073/pnas.91.19.9185
M3 - Article
C2 - 8090789
AN - SCOPUS:0028584245
SN - 0027-8424
VL - 91
SP - 9185
EP - 9189
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 19
ER -