New signaling pathways for hormones and cyclic adenosine 3',5'-monophosphate action in endocrine cells.
New signaling pathways for hormones and cyclic adenosine 3',5'-monophosphate action in endocrine cells.
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DOI：
10.1210/mend.15.2.0606
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发表时间：
2001-02
影响因子：
--
通讯作者：
J. Richards
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文献类型：
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作者：
J. Richards
糖蛋白激素、ACTH、TSH、FSH和LH调节内分泌细胞的多种功能。尽管cAMP和PKA长期以来一直被证明介导特定的细胞内信号事件，包括通过CREB-CBP复合物介导特定基因的转录，但最近的观察表明，PKA并不能解释cAMP的所有细胞内靶标。例如，TSH对甲状腺细胞增殖的刺激并不能被PKA抑制剂完全阻断。TSH和FSH可以通过PKAindependent但PI3-K/ pdk1 dependent途径刺激PKB磷酸化。FSH诱导激酶Sgk最近被证明是PKB的近亲。Sgk也是PI3-K-PDK1通路的靶点，这表明先前归因于PKB的一些作用可能是由这种诱导激酶介导的。具有鸟嘌呤核苷酸交换（GEF）活性的新型cAMP结合蛋白（cAMP- gefs; Epacs）的鉴定为cAMP的作用打开了新的大门，包括激活小的gtpase，如Rap1a， Rap2，可能还有Ras。这些gtpase是已知的下游激酶级联的激活剂，包括p38MAPK和Erk1/2以及PI3-K。因此，PKB和Sgk的FSH和TSH激活可能通过cAMP- gefs和PI3-K/PDK1通路的激活这一可选cAMP通路发生。
The glycoprotein hormones, ACTH, TSH, FSH, and LH regulate diverse functions in endocrine cells. Although cAMP and PKA have long been shown to mediate specific intracellular signaling events including the transcription of specific genes via the CREB-CBP complex, recent observations have indicated that PKA does not account for all of the intracellular targets of cAMP. For example, TSH stimulation of thyroid cell proliferation is not completely blocked by PKA inhibitors. TSH and FSH can stimulate PKB phosphorylation by a PKAindependent but PI3-K/PDK1-dependent pathway. An FSH inducible kinase, Sgk, has recently been shown to be a close relative of PKB. Sgk is also a target of PI3-K-PDK1 pathway, indicating that some effects previously ascribed to PKB may be mediated by this inducible kinase. The identification of novel cAMP-binding proteins that exhibit guanine nucleotide exchange (GEF) activity (cAMP-GEFS; Epacs) has open new doors for cAMP action that include activation of small GTPases such as Rap1a, Rap2, and possibly Ras. These GTPases are known activators of downstream kinase cascades, including p38MAPK and Erk1/2 as well as PI3-K. Thus, FSH and TSH activation of PKB and Sgk may occur via this alternative cAMP pathway that involves cAMP-GEFs and the activation of the PI3-K/PDK1 pathway.