p14–MP1-MEK1 signaling regulates endosomal traffic and cellular proliferation during tissue homeostasis

作者：David Teis, Nicole Taub, R Kurzbauer, Diana Hilber, Mariana E.G. de Araujo, Miriam Erlacher, Martin Offterdinger, Andreas Villunger, Stephan Geley, Georg Bohn, Christoph A. Klein, Michael W. Hess, Lukas Alfons Huber · 发表于：The Journal of Cell Biology · 年份：2006 · DOI：10.1083/jcb.200607025 · 被引用次数：210 · 研究领域：Retinal Development and Disorders、Cellular transport and secretion、Ubiquitin and proteasome pathways

The extracellular signal-regulated kinase (ERK) cascade regulates proliferation, differentiation, and survival in multicellular organisms. Scaffold proteins regulate intracellular signaling by providing critical spatial and temporal specificity. The scaffold protein MEK1 (mitogen-activated protein kinase and ERK kinase 1) partner (MP1) is localized to late endosomes by the adaptor protein p14. Using conditional gene disruption of p14 in mice, we now demonstrate that the p14-MP1-MEK1 signaling complex regulates late endosomal traffic and cellular proliferation. This function its essential for early embryogenesis and during tissue homeostasis, as revealed by epidermis-specific deletion of p14. These findings show that endosomal p14-MP1-MEK1 signaling has a specific and essential function in vivo and, therefore, indicate that regulation of late endosomal traffic by extracellular signals is required to maintain tissue homeostasis.