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 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.
Teis
David
D
Division of Cell Biology, Innsbruck Medical University, A-6020 Innsbruck, Austria.
Taub
Nicole
N
Kurzbauer
Robert
R
Hilber
Diana
D
de Araujo
Mariana E
ME
Erlacher
Miriam
M
Offterdinger
Martin
M
Villunger
Andreas
A
Geley
Stephan
S
Bohn
Georg
G
Klein
Christoph
C
Hess
Michael W
MW
Huber
Lukas A
LA
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D019426:Integrases; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; C426009:LAMTOR2 protein, mouse; C114559:Lamtor3 protein, mouse; D011506:Proteins; D066246:ErbB Receptors; D048369:MAP Kinase Kinase 1; C482127:Map2k1 protein, mouse; C045073:Cre recombinase; D019426:Integrases