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Directing NGF's actions: it's a Rap

Nature Cell Biology volume 7, pages 338–339 (2005)Cite this article

Epidermal growth factor and nerve growth factor (NGF) lead to significantly different temporal patterns of extracellular-signal-regulated kinase activation, and differential regulation of Ras and Rap1 have been implicated in mediating this temporal specificity. Now Sasagawa et al. derive a computational model that incorporates the known signalling interactions and identifies key points of regulation that control these processes.

The contrasting actions of NGF and epidermal growth factor (EGF) to differentiate or proliferate PC12 cells — a model for neuronal versus endocrine differentiation1 — has been used to develop a paradigm for growth factor specificity2. Early studies demonstrate that the duration of mitogen-activated protein (MAP) kinase signalling can dictate the biological outcome of these growth factors3. EGF, acting through the EGF receptor (EGFR), stimulates a rapid and transient activation of extracellular-signal-regulated kinases (ERKs) that is required for proliferation. In contrast, NGF, acting through the TrkA receptor, induces a sustained activation of ERKs that is required for differentiation4. Models for both the transient activation of ERKs by EGF and the sustained activation of ERKs by NGF have generally focused on the role of Ras and Ras effectors5.

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Figure 1: EGF and NGF lead to different kinetics of ERK activation.
Figure 2: The computational model takes into account many protein interactions, some of which are shown here.

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  1. the Oregon Health Sciences University, Vollum Institute L-474, 3181 SW Sam Jackson Park Road, Portland, 97201-3098, OR, USA

    Philip J. S. Stork

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Stork, P. Directing NGF's actions: it's a Rap. Nat Cell Biol 7, 338–339 (2005). https://doi.org/10.1038/ncb0405-338

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