Fig. 6.

Proposed model for the role of APP, phosphorylated at Thr668, in neurite outgrowth. Endogenous wild-type APP is phosphorylated at Thr668 after incubation with NGF, and PiAPP present in growth cones influences neurite extension via a putative protein factor (gray box). Exogenous wild-type APP is also phosphorylated in response to NGF treatment and contributes to normal neurite extension. Exogenous fAPP695T668A(T668A) cannot bind the putative protein, but neurite extension progresses normally by virtue of the interaction of endogenous phosphorylated APP with protein factor. In contrast, exogenous fAPP695T668E (T668E) binds the putative protein factor, but this association either initially blocks neurite outgrowth or interferes with normal function of the phospho-APP/protein factor complex by a “dominant negative” effect.