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. 2020 Aug 17;21(16):5906. doi: 10.3390/ijms21165906

Figure 2.

Figure 2

Prolidase-dependent EGFR- and HER2-downstream signaling. Prolidase binds to EGFR and HER2, evoking intracellular responses. (A) Under physiological conditions, direct binding of PEPD to EGF receptor results in the induction of pro-growth and pro-proliferation pathways such as phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR), extracellular signal-regulated kinase (ERK)1/2, and signal transducer and activator of transcription 3 (STAT3). (B) Under overexpression of EGFR, prolidase silences Akt, ERK1/2, and STAT3 pathways followed by internalization and degradation of the receptor. (C) PEPD affects upregulated HER2 via dissociation of HER2-Src complex, inhibition of Akt, ERK1/2 and STAT3 pathways, and induction of apoptosis. Red dots indicate prolidase and circled ‘P’ presents phosphorylation event. HER2—epidermal growth factor receptor 2, EGFR—epidermal growth factor receptor. Created with BioRender.com.