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Fig. 4 | Molecular Medicine

Fig. 4

From: Autosomal dominant polycystic kidney disease and pioglitazone for its therapy: a comprehensive review with an emphasis on the molecular pathogenesis and pharmacological aspects

Fig. 4

Illustration of the effects of polycystins dysfunctioning on EGFR and MAPK/ERK pathway. "Epidermal growth factor" (EGF) and "Insulin-like growth factor-1" (IGF-1) act as ligands for the epidermal growth factor receptor (EGFR). When gets activated by these ligands, dimerization of receptor is induced that leads to the activation of the tyrosine kinase activity of the receptor which further leads to the phosphorylation of tyrosine residues on each other (autophosphorylation) to form phosphotyrosine (shown by letter, 't'). The “growth factor receptor-bound protein-2” (GRB2) is an adaptor protein that helps to transduce the signals from EGFR to "Rouss avian sarcoma" (RAS) protein. GRB2 binds to phosphotyrosine and SOS protein via its SH2 and SH3 domains, respectively. The GRB2/SOS complex now activates the RAS. RAS in turn activates the RAF (protein kinase activity of RAF gets activated) that phosphorylates the mitogen-activated protein kinase kinase (MEK). MEK phosphorylates the extracellular signal-regulated kinase (ERK); also known as mitogen-activated protein kinase (MAPK) which further phosphorylates several other proteins that regulate cell proliferation, and differentiation. Decreased polycystin-1 expression lowers the activation threshold of the MAPK/ ERK pathway by IGF-1 and increased EGF-induced inward currents in kidney epithelial cell lines are produced due to over-expression of polycystin-2; together lead cystogenesis (Ma et al. 2005; Parker et al. 2007)

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