Divergence in the upstream signaling of nerve growth factor (NGF) and epidermal growth factor (EGF).

The early response of mammalian cells to growth factors consists of a combination of protein assemblages and kinase cascades. In the study of how signal specificity of different growth factors is determined, PC12 cells represent an elective experimental model to compare the signaling of differentiative nerve growth factor (NGF) and mitogenic epidermal growth factor (EGF). Focusing on Shc as established regulator of the Ras-ERK cascade, whose sustained activation is known to critically shape the neuronal differentiation of PC12 cells, the present manuscript describes two novel sources of divergence in the signaling of NGF and EGF: a differential phosphorylation of p66-Shc at early time points and a differential duration in the recruitment of the overall pool of Shc.