ANG II stimulates PKC-dependent ERK activation, DNA synthesis, and cell division in intestinal epithelial cells

Abstract

3 H]thymidine incorporation and a slight shift toward the S and G2/M phases of the cell cycle, whereas the combination of EGF and phorbol 12,13-dibutyrate (PDB) synergistically stimulated DNA synthesis. To investigate the effects of receptor-mediated PKC activation on mitogenesis, we demonstrated that ANG II induced ERK activation, a response completely blocked by pretreatment with mitogen/extracellular signal-regulated kinase inhibitors or specific PKC inhibitors. Furthermore, ANG II stimulated an over threefold increase in [3 H]thymidine incorporation that was corroborated by flow cytometric analysis of the cell cycle to levels comparable to that achieved by the combination of EGF and PDB. Taken together, our results indicate that receptor-mediated PKC activation, as induced by ANG II, transduces mitogenic signals leading to DNA synthesis and cell proliferation in IEC-18 cells.

Differential FAK phosphorylation at Ser-910, Ser-843 and Tyr-397 induced by angiotensin II, LPA and EGF in intestinal epithelial cells

“…ANG II binds to specific endogenous receptors in intestinal epithelial IEC-18 cells [44] and induces multiple signaling pathways and biological responses in these cells, including DNA synthesis and proliferation [45][46][47][48][49]. As shown by the results presented in Fig.1 A (control), stimulation with ANGII also markedly increased the migration of IEC-18 cells into the denuded area of a razor blade wound.…”

“…ANGII, acting through the G q -coupled AT 1 receptor, stimulates activation of ERK, protein kinase D and Pyk2 through a protein kinase C (PKC)-dependent pathway [46,48]. Here, we examined whether the increase in FAK Ser-910 phosphorylation in response to ANGII in IEC-18 cells is mediated through a PKC/ERK-dependent pathway.…”

Biphasic Regulation of Yes-associated Protein (YAP) Cellular Localization, Phosphorylation, and Activity by G Protein-coupled Receptor Agonists in Intestinal Epithelial Cells

“…These cells endogenously express G␣ q/11 -coupled receptors for angiotensin II (ANG II) and vasopressin (23,39,40,(43)(44)(45)(46) and have been extensively used as a model system to examine signal transduction pathways in response to GPCR activation (23,36,38,39,(43)(44)(45)47). ANG II and vasopressin act as potent growth factors for IEC-18 and IEC-6 cells (23,39,(43)(44)(45)47). Because the levels of YAP/TAZ influence their association with transcriptional cofactors especially when expressed at elevated levels, we studied the localization, phosphorylation, and activity of the endogenous YAP protein.…”

Angiotensin II and Epidermal Growth Factor Induce Cyclooxygenase-2 Expression in Intestinal Epithelial Cells through Small GTPases Using Distinct Signaling Pathways

“…Angiotensin II (Ang II) stimulates ion transport in both the small and large intestines through Ang II type 1 (AT 1 ) receptors located on epithelial cells (36,37). We recently demonstrated that Ang II, one of the most potent regulators of blood pressure, induces proliferation and DNA synthesis in IEC-18 cells (39). We showed that Ang II, acting through the G q -coupled AT 1 receptor, stimulates protein kinase C-dependent ERK, protein kinase D, and tyrosine phosphorylation of Pyk2 (38 -40).…”