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. Author manuscript; available in PMC: 2016 Oct 21.
Published in final edited form as: Oncogene. 2015 Aug 3;35(16):2075–2086. doi: 10.1038/onc.2015.269

Figure 8. Model for bimodal regulation of epithelial cell proliferation by AREG.

Figure 8

Proteolytic cleavage of the membrane-bound AREG precursor (proAREG) results in the release of soluble AREG that binds and activates EGFR ultimately promoting G1/S progression via pathways that involve classical MEK/ERK signaling, cyclin D1 phosphorylation of Rb and activation of E2F family transcription factors. A second, as yet not completely characterized intracellular pathway, possibly involving the proAREG cytoplasmic domain, supports a separate FoxM1-dependent program necessary for G2/M transition and cytokinesis.