PC12 Cell stimulation leads to distinct outcomes upon stimulation with either EGF or NGF (epidermal and nerve growth factors). The outputs are transmitted through the MAPK/ERK signaling pathway; stimulation with EGF causes transient activation of the ERK, via a negative feedback loop, leading to cell proliferation whereas stimulation with NGF leads to sustained activation of ERK, via a positive feedback loop, leading to differentiation.


How does the signaling pathway know which kind of feedback loop to initiate at the ERK level from upstream stimulation by EGF or NGF?

Helpful Image to explain question

To reiterate: I want to figure out how EGF binding at the membrane level triggers negative feedback downstream, and NGF binding triggers positive feedback?

A link to the image is (http://www.nature.com/nrm/journal/v12/n2/fig_tab/nrm3048_F4.html)

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