Figure 3. Hyperactive SCF/c-kit pathways in the Nf1^+/- mast cell.

Kit-ligand (SCF) binding at the c-kit receptor tyrosine kinase induces receptor dimerization, activates Ras to its GTP-bound conformation, and induces Ras-Raf-Mek-Erk and PI-3K-Rac-Pak-p38 signaling pathways. While Mek-Erk signals may principally mediate mast cell proliferation, PI-3K mediates survival, motility and, through its Pak-dependent crosstalk with Raf-Mek, proliferation. Nf1 accelerates the intrinsic hydrolysis of Ras-GTP to inactive Ras-GDP and serves, at least in part, to negatively regulate Mek-Erk- and PI-3K-directed pathways. Although SCF-c-kit interactions initiate other molecular events (e.g. Akt-mTOR), this schematic highlights only those thus far shown to be hyperactivate in the Nf1^+/- mast cell. Dashed lines indicate multiple downstream effectors not fully detailed.