The phosphatidylinositol 3-kinase α is required for DNA synthesis induced by some, but not all, growth factors

Serge Roche, Manfred Koegl, Sara Courtneidge

Research output: Contribution to journalArticle

252 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9185-9189
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number19
DOIs
Publication statusPublished - Sep 13 1994
Externally publishedYes

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Keywords

  • microinjection
  • protein-tyrosine kinases
  • signal transduction

ASJC Scopus subject areas

  • Genetics
  • General

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