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 Citations (Scopus)

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
StatePublished - Sep 13 1994
Externally publishedYes

Fingerprint

Phosphatidylinositol 3-Kinase
Intercellular Signaling Peptides and Proteins
DNA
Platelet-Derived Growth Factor Receptors
Lysophosphatidic Acid Receptors
Bombesin
Macrophage Colony-Stimulating Factor
Antibodies
Platelet-Derived Growth Factor
Receptor Protein-Tyrosine Kinases
S Phase
GTP-Binding Proteins
Epidermal Growth Factor Receptor
Fibroblasts

Keywords

  • microinjection
  • protein-tyrosine kinases
  • signal transduction

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

@article{8dd3dc02a593451e8229db4626df1a97,
title = "The phosphatidylinositol 3-kinase α is required for DNA synthesis induced by some, but not all, growth factors",
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.",
keywords = "microinjection, protein-tyrosine kinases, signal transduction",
author = "Serge Roche and Manfred Koegl and Sara Courtneidge",
year = "1994",
month = "9",
day = "13",
doi = "10.1073/pnas.91.19.9185",
language = "English (US)",
volume = "91",
pages = "9185--9189",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "19",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=0028584245&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028584245&partnerID=8YFLogxK

U2 - 10.1073/pnas.91.19.9185

DO - 10.1073/pnas.91.19.9185

M3 - Article

C2 - 8090789

AN - SCOPUS:0028584245

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

SN - 0027-8424

IS - 19

ER -