Weston W M, Potchinsky M B, Lafferty C M, Ma L, Greene R M
Department of Pathology, Anatomy, and Cell Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
In Vitro Cell Dev Biol Anim. 1998 Jan;34(1):74-8. doi: 10.1007/s11626-998-0056-3.
Signaling pathways utilized by EGF, cAMP, and TGF beta have been demonstrated to play critical roles in normal palate development. Stimulation of these pathways has been shown in palate cells and numerous other systems to affect cell growth. Because proper regulation of cell growth is critical to palate development, we speculate that fine regulation of palatal cell growth may be accomplished through crosstalk between these signaling pathways. We therefore set out to determine the effects of cAMP and TGF beta on EGF-induced cell proliferation in murine embryonic palate cells. We found that both TGF beta and cAMP inhibited the proliferative response of cells to treatment with EGF, whereas H89, a serine/ threonine protein kinase inhibitor with selectivity towards cAMP-dependent protein kinase, increased the cells' proliferative response to EGF. Genestein, a selective inhibitor of tyrosine kinases, at high doses abrogated the cells' proliferative response to EGF, confirming that EGF's ability to induce cell proliferation is critically dependent upon tyrosine kinase activity. Lower doses of genestein, however, actually enhanced cellular response to EGF. The data suggest that both the TGF beta- and cAMP-mediated signaling pathways may be involved in modulation of the effects of EGF on palate cell growth in vivo.
表皮生长因子（EGF）、环磷酸腺苷（cAMP）和转化生长因子β（TGFβ）所利用的信号通路已被证明在正常腭发育中起关键作用。在腭细胞和许多其他系统中，这些信号通路的激活已显示会影响细胞生长。由于细胞生长的适当调节对腭发育至关重要，我们推测腭细胞生长的精细调节可能通过这些信号通路之间的相互作用来实现。因此，我们着手确定cAMP和TGFβ对小鼠胚胎腭细胞中EGF诱导的细胞增殖的影响。我们发现，TGFβ和cAMP均抑制细胞对EGF处理的增殖反应，而H89，一种对cAMP依赖性蛋白激酶具有选择性的丝氨酸/苏氨酸蛋白激酶抑制剂，则增加了细胞对EGF的增殖反应。染料木黄酮，一种酪氨酸激酶的选择性抑制剂，高剂量时消除了细胞对EGF的增殖反应，证实了EGF诱导细胞增殖的能力严重依赖于酪氨酸激酶活性。然而，较低剂量的染料木黄酮实际上增强了细胞对EGF的反应。数据表明，TGFβ和cAMP介导的信号通路可能都参与了体内EGF对腭细胞生长影响的调节。
