FIG 9.

Schematic model of how SH2B1β enhances gene expression and neuronal differentiation through STAT3 (step 1). After FGF1 stimulation, SH2B1β and STAT3 interact with FGFR1 (step 2). SH2B1β subsequently interacts with STAT3 (step 3) and transports STAT3 to the nucleus (step 4). SH2B1β and STAT3 dissociate, followed by the formation of STAT3-STAT3 dimers and/or STAT3-Sp1 heterodimers, both of which bind to the promoter regions of differentiation genes, such as Egr1 (step 5) and Cdh2 (step 6). In a parallel pathway, phosphorylated STAT3 forms a homodimer and shuttles to the nucleus in response to FGF1 stimulation (step 7). SH2B1β may regulate a putative serine kinase (K) that phosphorylates STAT3. Solid line, known pathways or pathways identified in this study; dashed line, putative steps.