Signaling by fibroblast growth factors: the inside story

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Polypeptide growth factors, including fibroblast growth factors (FGFs), are known to bind cell surface receptors.
• Receptor activation typically initiates intracellular signaling cascades via protein kinases.
• A subset of researchers has investigated non-canonical, intracellular roles for FGFs for over a decade.

Purpose of the Study:

• To review the emerging evidence for direct intracellular actions of fibroblast growth factors (FGFs).
• To highlight recent findings that support alternative signaling pathways for FGFs.
• To discuss the implications of intracellular FGF signaling for future research and therapeutic development.

Main Methods:

• Literature review of recent publications on fibroblast growth factor (FGF) signaling.
• Analysis of studies reporting direct intracellular targets of FGF and FGF-like proteins.
• Synthesis of evidence supporting non-canonical intracellular FGF actions.

Main Results:

• Two recent publications provide specific evidence for intracellular targets of FGF and FGF-like proteins.
• These findings support the existence of direct intracellular signaling pathways for FGFs.
• The concept of intracellular FGF actions is transitioning from a "counterculture" view to mainstream scientific acceptance.

Conclusions:

• The traditional model of FGFs acting solely through cell surface receptors is being challenged.
• Direct intracellular targets for FGFs have been identified, suggesting novel signaling mechanisms.
• These discoveries open new avenues for understanding FGF functions and developing targeted therapies.