Src is required for cell migration and shape changes induced by fibroblast growth factor 1

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Fibroblast growth factor 1 (FGF-1) is a key signaling molecule involved in various cellular processes.
• Cortactin is a cortical actin-associated protein crucial for cytoskeletal dynamics.
• The protein tyrosine kinase Src plays a significant role in cellular signaling pathways.

Purpose of the Study:

• To investigate the role of Src in FGF-1-induced cortactin tyrosine phosphorylation.
• To elucidate the specific contribution of Src and cortactin to FGF-1-mediated cellular responses.
• To differentiate the roles of Src in FGF-1-induced mitogenesis versus cell migration and shape change.

Main Methods:

• Utilized Src knockout (Src-/-) mouse cells.
• Performed in vitro kinase assays to assess tyrosine phosphorylation.
• Conducted morphological analyses, including lamellipodia formation and cortactin localization.
• Examined the phosphorylation of Snt/Frs2, an early FGF-1 signaling protein.

Main Results:

• FGF-1 induces cortactin tyrosine phosphorylation, requiring specific tyrosine residues targeted by Src.
• Src is essential for FGF-1-induced cortactin phosphorylation in cells.
• Src deficiency impairs FGF-1-mediated cell shape change and migration, but not proliferation.
• FGF-1 fails to induce lamellipodia formation and cortactin translocation to the leading edge in Src-/- cells.
• The early FGF-1 signaling pathway via Snt/Frs2 to Ras remains unaffected by Src deficiency.

Conclusions:

• Src and cortactin are integral components of the FGF-1 signaling pathway regulating cell migration and shape.
• Src-mediated cortactin phosphorylation is critical for FGF-1-induced cytoskeletal rearrangements.
• The identified pathway is distinct from the FGF-1-driven mitogenic response.