EC secretion of EGFR ligands anchored bcr-abl in the membrane precursors.8 However, EGFR can be transactivated by the ligands by TGF b pathways.17 release independent A previous study also found that TGF transactivates b1 EGFR in NRK 49F cells, 16 although they are not to study the biological significance of EGFR transactivation. in this respect is the canonical TGF b1 signaling the activation of TGF bR and downstream rts Smad2/3.34 We found that TGF b1 phosphorylation of Smad2 / 3 obtained by the TGF bR ht. In addition, TGF b1 was activated Smad2 / 3 dependent Ngig of p38 kinase, but not EGFR or ERK1 / 2 This finding is Similar to two previous studies showing that TGF b1 activated Smad2 / 3 on p38 kinase h Depends fibroblasts.15, 35 The biological significance of the relationship between EGFR and noncanonical ERK1 / 2 and p38 kinases in the TGF b-induced effects was investigated in this study. In this respect, ERK1 / 2 and p38 kinase by TGF-b is either activated or quickly found that TGF b1 both ERK1 / 2 and p38 kinase in NRK 49F cells rapidly activates slowly.36We. In addition, TGF b1 ERK1 / 2 and p38 activated kinase are dependent Ngig of TGF-BIZ kinase and EGFR kinase. This finding, together with the finding that the TGF b1-induced activation of EGFR were tt than that of ERK1 / 2 and p38 kinase, suggesting that ksp proteinERK1 / 2 and p38 kinase activated by TGFB1 way of EGFR. The mechanism of cell mitogenesis by TGF B1 was induced also been investigated in this study. showed in this context, a recent study that Smad2 / 3 for the B1 cell mitogenesis induced TGF fibroblasts.37 however necessary, we found that TGF-induced mitogenesis depends ngig from cell B1 kinase TGF b1 and EGFR kinase. This is consistent with a previous study showed that the density of EGFR contr Dampen the mitogenic activation of NRK 49F cells by EGF.25 Interestingly, gefitinib st Stronger than SB431542, TGF-b1-induced mitogenesis d Was. This l sst By the fact that some TGF binduced mitogenesis in renal fibroblasts by ALK1.
Abl, which is also activated by EGFR.38 We also found that TGFB1-induced cyclin D1 protein expression h Depends mediated explained utert the EGFR kinase. This is consistent with two earlier studies that show that EGF expression of cyclin D1 protein in fibroblasts23 and that G protein-coupled receptors induces the expression of cyclin D1 protein h EGFR.24 depends To the biological significance of the study induced ERK1 / 2 and p38 kinase in TGF-b-induced effects, we found that TGFB1-induced mitogenesis of ERK1 / 2 and p38 kinase-dependent depends. This finding is the notion compatiblewith thatERK1 / 2 is usually associated with the cell proliferation39 and will show from a previous study that the proliferation of fibroblasts h Depends ERK2.28 same theEGFR ERK1 / 2 signaling pathway for certain effects induced in keratinocytes TGF b is necessary supported. 17 In contrast, p38 kinase, as a rule with inhibition of proliferation in many cells.40 are associated, have shown two new studies that TGF-b1 induced proliferation dependent Ngig of p38 kinase is in fibroblasts.29, 41 A schematic representation of the mitogenesis by TGF b NRK-49F cells induced is shown in Figure 10. Endometrial cancer is h Themost frequently malignancy T of the female genital tract in industrialized L Change diagnosed.