Methodology 

This study focused on exploring the intracellular signaling pathways initiated by FGF2, with a major focus on the Mitogen-Activated Protein Kinase (MAPK) signaling cascade. The conceptual framework for this analysis is presented in Figure 1, which models the activation sequence following FGF2 binding to its cognate receptor, FGFR. This binding event triggers receptor phosphorylation, initiating downstream signal flow through MEK 1/2 to ERK 1/2, which eventually indirectly activates cell proliferation and cell reprogramming.

Furthermore, the model outlines parallel pathways activated by FGFR, including the PI3K/AKT pathway, the p38 MAPK pathway, the JNK pathway, and the PKC pathway.

To experimentally test the specific contributions of these kinases and pathways, a suite of pharmacological inhibitors targeting distinct nodes was utilized. As indicated by red highlighting in Figure 1, these interventions included: PD173074 targeting the FGFR itself; U0126 and/or PD98059 targeting MEK1/2 activity; Dasatinib and/or FR180204 targeting ERK1/2 activity; LY294002 targeting PI3K; SB203580 targeting p38; SP600125 targeting JNK; and GF-109203X targeting PKC. The schematic uses standard conventions where arrows denote activation and hammer-ended lines exhibit inhibition. While the MAPK/ERK pathway was the major emphasis of our investigation, the PI3K pathway was also examined, primarily through the application of its inhibitor, LY294002.