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Figure 6 | Molecular Cancer

Figure 6

From: Inhibition of Rho-associated coiled-coil containing protein kinase enhances the activation of epidermal growth factor receptor in pancreatic cancer cells

Figure 6

A schematic representation of the involvement of ROCK in the EGFR signaling in pancreatic cancer cells. First, EGF binds to the EGFR on the cell surface, and the EGFR undergoes dimerization and autophosphorylation at tyrosine residues. This triggers EGFR-related downstream signaling, such as activation of the MEK1/2-p44/p42 MAPK or Akt pathways, within 5 min of EGF stimulation (). Around 5 min after the start of stimulation, EGF starts to induce the activation of RhoA and subsequently ROCK, as demonstrated by upregulation of the phosphorylation of cofilin and MLC (). Inhibition experiments using Y27632 or siRNA indicated that activated ROCK cancels the persistent activation of the EGFR and the downstream pathways of MEK1/2 and Akt beginning at 5 min after the initiation of stimulation. Thus, ROCK functions to switch off the EGFR signaling that induces pancreatic cancer cell proliferation. EGF: epidermal growth factor, EGFR: EGF receptor, ROCK: Rho-associated coiled-coil containing protein kinase, MAPK: mitogen-activated protein kinase, GSK-3β: glycogen synthase kinase-3β, MLC, myosin light chain, P: phosphorylation, Y: tyrosine.

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