REGULATION OF HORMONE RESPONSIVENESS DURING CELLULAR DIFFERENTIATION

胰高血糖素反应性在狗肾细胞系中选择性丧失， MDCK细胞，经Harvey鼠肉瘤转化后， 通过在培养皿中培养细胞，可以恢复转化细胞的损失。 存在各种诱导剂，包括丁酸盐和前列腺素E2。 的 各种PG类似物诱导胰高血糖素敏感性的能力与 这与它们在转化细胞中激活环AMP的能力密切相关。 在 事实上，8-Br-环AMP也是一种有效的诱导剂，因此， PGE 2似乎是由cAMP介导的。 之前我们已经证明， PGE 2诱导被血清因子和TPA（佛波酯）抑制。 最近，我们发现表皮生长因子，在1 nM的浓度， 也抑制PGE 2的诱导。 我们还发现， EGF受体在诱导胰高血糖素反应时变得脱敏， EGF的作用 我们的研究结果表明，PGF 2和EGF之间的相互作用 在受体水平。 EGF依赖的受体磷酸化是 很好地建立了。 cAMP对EGF受体的磷酸化作用 依赖性激酶已被其他人证实。 人们很容易猜测 细胞分化的状态是由 EGF受体，它反过来又由特定的模式， 磷酸化 我们目前的努力是确定这些磷酸化的 EGF受体在不同的诱导条件下

Glucagon responsiveness was selectrively lost in a dog kidney cell line, MDCK cells, after transformation by Harvey murine sarcoma vitus and this loss can be restored to the transformed cells by culturing the cells in the presence of various inducers, including butyrate and protaglandin E2. The ability of various PG analogs to induce glucagon sensitivity correlates closely with their ability to activate cyclic AMP in transformed cells. In fact, 8-Br-cyclic AMP is also an potent inducer, therefore, induction by PGE2 seems to be mediated by cyclic AMP. Previously we have shown that PGE2 induction is inhibited by a serum factor and TPA, a phorbol ester. Recently, we found that epidermal growth factor, at a concentration of 1 nM also inhibits the induction by PGE2. We have also found that during the induction of glucagon response, EGF receptors become desensitized in their ability to bind EGF. Our results suggest an interplay between PGF2 and EGF at the receptor level. EGF-dependent phosphorylation of its receptor is well established. The phosphorylation of EGF receptors by cyclic AMP dependent kinase has been shown by others. It is tempting to speculate that the state of cellular differentiation is governed by the expression of EGF receptors which are regulated in turn by specific patterns of phyosphorylation. Our current effort is to define these phosphorylation of EGF receptors under various induction conditions.