Bruhn Maressa A, Pearson Richard B, Hannan Ross D, Sheppard Karen E
Growth Control and Differentiation Program, Peter MacCallum Cancer Centre, Melbourne, 3002, Victoria, Australia.
Growth Factors. 2010 Dec;28(6):394-408. doi: 10.3109/08977194.2010.518616. Epub 2010 Oct 5.
The serum and glucocorticoid kinase (SGK) family of serine/threonine kinases consists of three isoforms, SGK-1, SGK-2 and SGK-3. This family of kinases is highly homologous to the AKT kinase family, sharing similar upstream activators and downstream targets. SGKs have been implicated in the regulation of cell growth, proliferation, survival and migration: cellular processes that are dysregulated in cancer. Furthermore, SGKs lie downstream of phosphoinositide-3-kinase (PI3Kinase) signalling and interact at various levels with RAS/RAF/ERK signalling, two pathways that are involved in promoting tumorigenesis. Recent evidence suggests that mutant PI3Kinase can induce tumorigenesis through an AKT-independent but SGK3-dependent mechanism, thus implicating SGKs as potential players in malignant transformation. Here, we will review the current state of knowledge on the regulation of the SGKs and their role in normal cell physiology and transformation with a particular focus on SGK3.
丝氨酸/苏氨酸激酶的血清和糖皮质激素激酶（SGK）家族由三种亚型组成，即SGK-1、SGK-2和SGK-3。该激酶家族与AKT激酶家族高度同源，共享相似的上游激活因子和下游靶点。SGK已被证明参与细胞生长、增殖、存活和迁移的调控，而这些细胞过程在癌症中会失调。此外，SGK位于磷酸肌醇-3-激酶（PI3激酶）信号通路的下游，并在多个层面与RAS/RAF/ERK信号通路相互作用，这两条通路都参与促进肿瘤发生。最近的证据表明，突变的PI3激酶可通过一种不依赖AKT但依赖SGK3的机制诱导肿瘤发生，因此表明SGK是恶性转化中的潜在参与者。在此，我们将综述关于SGK调控及其在正常细胞生理学和转化中的作用的当前知识状态，特别关注SGK3。
