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  • Title: Cisplatin induces apoptosis through the ERK-p66shc pathway in renal proximal tubule cells.
    Author: Clark JS, Faisal A, Baliga R, Nagamine Y, Arany I.
    Journal: Cancer Lett; 2010 Nov 28; 297(2):165-70. PubMed ID: 20547441.
    Abstract:
    The extracellular signal-regulated kinase (ERK) has been shown to mediate cisplatin (CP)-induced toxicity to renal proximal tubule cells. Here, we demonstrate that ERK serves as the kinase that phosphorylates the pro-apoptotic p66shc protein at its Serine36 residue in CP-treated renal proximal tubule cells. Pharmacologic or dominant-negative inhibition of ERK mitigates cisplatin-induced Ser36 phosphorylation of p66shc. Overexpression of p66shc exacerbates while its knockdown or mutation of the Serine36 site to alanine ameliorates CP-induced nephrotoxicity in vitro. Since p66shc is Serine36 phosphorylated in the kidneys of mice after treatment with CP, a similar mechanism might exist in vivo.
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