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Phosphoinositides and cell proliferation.

M J Berridge, K D Brown, R F Irvine

    Journal of Cell Science. Supplement
    |January 1, 1985
    PubMed
    Summary
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    Growth factors stimulate inositol lipid hydrolysis, producing diacylglycerol (DG) and inositol trisphosphate (IP3) second messengers. Swiss 3T3 cells show increased inositol 1,3,4-trisphosphate, potentially regulating long-term cell growth.

    Area of Science:

    • Cell signaling pathways
    • Molecular biology
    • Biochemistry

    Background:

    • Growth factors initiate cellular responses via signal transduction pathways.
    • Inositol lipid hydrolysis generates key second messengers, diacylglycerol (DG) and inositol trisphosphate (IP3).
    • These messengers regulate intracellular events like pH changes, calcium mobilization, and protein kinase activation.

    Purpose of the Study:

    • To investigate the specific isomers of inositol trisphosphate (IP3) generated by growth factors.
    • To explore the potential roles of these IP3 isomers in cell growth regulation.
    • To understand the signaling mechanisms of growth factors, including those acting independently of inositol lipids.

    Main Methods:

    • Studies were conducted on Swiss 3T3 cells.

    Related Experiment Videos

  • Analysis of inositol lipid hydrolysis products.
  • Measurement of inositol trisphosphate isomer levels.

    • Main Results:

    • Growth factors stimulate the production of two IP3 isomers: inositol 1,4,5-trisphosphate and inositol 1,3,4-trisphosphate.
    • A significant increase in inositol 1,3,4-trisphosphate was observed.
    • Inositol 1,4,5-trisphosphate elevates intracellular calcium, while the function of inositol 1,3,4-trisphosphate remains to be elucidated but may relate to long-term events.

    Conclusions:

    • Growth factor signaling involves a bifurcating pathway utilizing IP3/Ca2+ and DG/C-kinase.
    • The slow turnover of inositol 1,3,4-trisphosphate suggests a role in long-term cellular processes, potentially including cell growth.
    • Understanding these pathways provides a framework for investigating oncogene mechanisms.