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Signaling molecules that mediate the actions of FGF

S D Demo1, A Kikuchi, K G Peters

  • 1Department of Medicine, University of California, San Francisco 94143-0130, USA.

Princess Takamatsu Symposia
|January 1, 1994
PubMed

Insights

Fibroblast growth factor (FGF) signaling is crucial for development. Studies show FGF receptor and RAS-interacting protein (RIP) are vital for lung and posterior structure formation in model organisms.

Area of Science:

  • Developmental Biology
  • Molecular Biology
  • Cell Signaling

Background:

  • Fibroblast growth factor (FGF) signaling regulates critical cellular processes like growth and differentiation.
  • FGF signaling pathways are essential for embryonic development, influencing tissue formation and patterning.

Purpose of the Study:

  • To investigate the role of FGF signaling and its receptor in lung development.
  • To elucidate the intracellular pathways mediating FGF's developmental effects, including the involvement of RAF and RAS.
  • To identify novel proteins that interact with RAS and mediate its function in FGF signaling.

Main Methods:

  • Utilized transgenic mice with dominant-negative FGF receptor in lung tissue to assess FGF's role in lung development.
  • Employed Xenopus embryos to study FGF's role in posterior structure development and mesoderm induction.
  • Investigated the function of serine-threonine kinase RAF and RAS GTP-binding protein in FGF signaling pathways.
  • Identified and characterized a novel RAS-interacting protein (RIP) with a RAS-binding domain.

Main Results:

  • Dominant-negative FGF receptor expression in mouse lungs resulted in failure of lung development, highlighting FGF's importance in airway branching and alveolar formation.
  • In Xenopus, FGF is involved in posterior structure development, with RAF mediating mesoderm induction; dominant-negative RAF blocked FGF's action, while activated RAF enhanced posterior development.
  • Identified RIP, a novel gene encoding a RAS-binding domain, similar to ralGDS, suggesting RIP and ralGDS are mediators of RAS function in FGF signaling.

Conclusions:

  • FGF signaling is indispensable for lung development, specifically for airway branching and alveolar formation.
  • RAF and RAS are key intracellular mediators of FGF's developmental roles, influencing mesoderm induction and posterior structure formation.
  • RIP represents a novel component in the RAS-mediated signaling cascade downstream of FGF, contributing to the understanding of FGF's broader developmental functions.

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