Cell-cycle kinases to control endocytosis.

胰岛素信号传导由位于靶细胞表面的受体酪氨酸激酶（RTK）启动。在胰岛素结合后，活化的复合物迅速内化到内体装置中。以前，内吞作用被认为是减少受体信号传导的手段，因此允许对顺序信号传导事件的适当响应。然而，活性信号传导在RTK内化后可能会继续很好地进行，并且内吞途径的选择通常可以决定响应。尽管胰岛素信号转导的生物学证据广泛，但内吞作用在决定其生理结果中的机制和作用仍然不清楚。高尔基体/内体组分的蛋白质组学调查最近表明，很少有尚未被表征的机制从基础系统中借用元素来调节RTK路由。使用小鼠基因组信息学（MGI）设施进行的生物信息学分析显示了已知参与胰岛素受体（IR）信号传导的蛋白质与特定细胞功能和机制之间的功能联系网络。我们最近已经证实，Cdk 2库在核内体中被区室化，在核内体中它与配偶体缔合并控制胰岛素内化（Fiset等人，2011 Cellular Signaling 23：911-919）。我们假设未表征的基于内体的蛋白质复合物已经获得了亚功能，并与胰岛素作用协调IR路由。我们还假设存在一个新的领导机制控制胰岛素的作用：Cdk 2复合物驻留在核内体上，在那里他们将被理想地定位到参与当地的监管电路协调IR信号和贩运事件。

Insulin signaling is initiated by a receptor tyrosine kinase (RTK) located at the surface of target cells. Following insulin binding, there is rapid internalization of the activated complexes into the endosomal apparatus. Previously, endocytosis was thought to be a means to diminish the receptor signaling and hence allowing an appropriate response to sequential signaling events. However, active signaling may continue well after RTK internalization and the choice of endocytic routing can often determine the response. Despite the wide-ranging biological evidences of insulin signaling, the mechanism and role of endocytosis in determining its physiological outcome is still not understood. Proteome surveys of Golgi/endosomes fractions suggested recently that few and yet to be characterized mechanisms borrow elements from fondamental systems to regulate RTKs routing. Ongoing bioinformatics analyses using Mouse Genome Informatics (MGI) facilities show a network of functional links between proteins known to be involved in insulin receptor (IR) signaling and specific cellular functions and mechanisms. We have recently confirmed that a pool of Cdk2 is compartmentalized in endosomes where it associates with partners and controls insulin internalization (Fiset et al. 2011 Cellular Signaling 23: 911-919). We hypothesize that uncharacterized endosome-based protein complexes have acquired subfunctionality and coordinate IR routing with insulin action. We also hypothesize the presence of a new leader mechanism controlling insulin action: Cdk2 complexes reside on endosomes where they would be ideally positioned to participate in local regulatory circuits coordinating IR signaling and trafficking events.