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

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 k...

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Bibliographic Details
Published in:The Journal of cell biology 2006-12, Vol.175 (6), p.861-868
Main Authors: Teis, David, Taub, Nicole, Kurzbauer, Robert, Hilber, Diana, de Araujo, Mariana E, Erlacher, Miriam, Offterdinger, Martin, Villunger, Andreas, Geley, Stephan, Bohn, Georg, Klein, Christoph, Hess, Michael W, Huber, Lukas A
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - metabolism
Animals
Antibodies
Biochemistry
Biological transport
Cell Proliferation
Cellular biology
Embryo, Mammalian - cytology
Embryo, Mammalian - metabolism
Embryos
Endosomes
Endosomes - metabolism
Epidermal cells
Epidermis
Epidermis - cytology
Epidermis - metabolism
Fluorescent antibody techniques
Gene expression regulation
Integrases
Kinases
MAP Kinase Kinase 1 - metabolism
Mice
Mice, Knockout
Proteins
Proteins - genetics
Proteins - physiology
Receptor, Epidermal Growth Factor - metabolism
Scaffolds
Signal Transduction
Skin
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Summary: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.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200607025