Fig. 2

Schematic diagram depicting modulation of the FGF signaling cascade by different isoforms of hSEF. The transmembrane form of Sef (hSEF-a), physically associates with FGFR1 and FGFR2 to restrict FGFR kinase activation and subsequent FRS2α phosphorylation upon FGF stimulation. By inhibiting FGFR mediated FRS2α tyrosine phosphorylation as well as subsequent adaptor protein activation, the ERK and AKT pathways are attenuated. hSEF-a is also reported to bind to the MEK-ERK complex without inhibiting activation of its components, but impedes dissociation and nuclear translocation of ERK and thus activation of its downstream targets. Conversely, the cytosolic hSef-b isoform specifically restricts ERK phosphorylation. hSef-a also regulates the activation of the p38 MAPK pathway in a cell type specific manner; and promotes the activation of the JNK pathway by associating with TAK1. The cytosolic hSef-S isoform regulates cellular proliferation through an undefined mechanism