Contribution of PKC-dependent and -independent processes in temporal ERK regulation by ET-1, PDGF, and EGF in rat myometrial cells

Abstract

Endothelin-1 (ET-1), platelet-derived growth factor (PDGF), and epidermal growth factor (EGF) stimulated thymidine incorporation with different efficiency (PDGF >> EGF = ET-1) in rat myometrial cells. They also stimulated ERK activation, which culminated at 5 min and then declined to reach a plateau (at 45 min: EGF > 90%, PDGF = 50%, and ET-1 < 10% of maximum). Inhibition and downregulation of PKC demonstrated that ERK activation at 5 min involved PKC delta and -zeta for ET-1 and PKC alpha plus another PKC isoform for PDGF. By contrast, the EGF response did not involve PKC. Stimulation of Ras was more important with EGF than with PDGF, with ET-1 being the weakest activator. The simultaneous incubation of the cells with EGF and ET-1 potentiated the ERK activation at 5 min and mimicked the plateau phase obtained with PDGF. Under these conditions thymidine incorporation was comparable to that induced by PDGF. Taken together, our results indicated that the kinetic profile of ERK activation and its impact on cell proliferation can be modulated by the differential involvement of PKC isoforms and the amplitude of Ras activation.

A role for PDGF signaling in expansion of the extra-embryonic endoderm lineage of the mouse blastocyst

“…In conclusion, our data support a model whereby PDGF pathway signaling via MEK 3369 RESEARCH ARTICLE PDGF signaling promotes expansion of ExEn and PKC plays a key role in XEN cell propagation. However, the exact and respective roles of MEK and PKC remain unclear, and we cannot exclude cross-talk, as has been reported in various cell systems (Lee et al, 2006;Okazaki et al, 2000;Robin et al, 2004). Future studies will be required to address the specific and combinatorial roles of these signal transducers.…”

Transactivation of the epidermal growth factor receptor in responses to myocardial stress and cardioprotection

“…Clerk et al 2006 found that EGF increases cardiomyocyte Ras.GTP and activates c-Raf and ERK1/2 phosphorylation independently of PKC. Similarly, there is evidence that EGF activation of ERK1/2 in non-cardiac muscle is PKC-independent and Ras-dependent (Robin et al, 2004). These findings suggest that direct ligation of the EGFR removes the PKC dependence of signalling, implicating upstream functions of the kinase in regulating ligand levels and EGFR phosphorylation.…”

Hormonal signaling and signal pathway crosstalk in the control of myometrial calcium dynamics

“…EGF also activates the PI-3 kinase/Akt pathway in other tissues, synergizing with PLCγ activity in mediating EGF effects [27]. EGF activation of ERK in myometrium is PKC-independent and involves the conventional Ras pathway [28]. EGF has also been implicated in myometrial cell proliferation in a pathway involving PKC and eicosanoids [29].…”