Localization of the MP1-MAPK scaffold complex to endosomes is mediated by p14 and required for signal transduction.
Eukaryotic cells use the extracellular signal regulated kinase (ERK) cascade to connect cell-surface receptors to intracellular targets. Although various signals are routed through the ERK pathway, cells respond accordingly to a given stimulus. To regulate proper signal transduction, scaffolds and adaptors are employed to organize specific signaling units. The scaffold protein MP1 (MEK1 partner) assembles a scaffold complex in the ERK cascade. We show that p14 functions as an adaptor protein, which is required and sufficient to localize MP1 to endosomes. Reduction of MP1 or p14 protein levels by siRNAi results in defective signal transduction. Therefore, our results suggest that the endosomal localization of the p14/MP1-MAPK scaffold complex is crucial for signal transduction.
Teis
David
D
Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
Wunderlich
Winfried
W
Huber
Lukas A
LA
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000494:pharmacology; D005057:Eukaryotic Cells / Q000166:cytology / Q000378:metabolism*; D006367:HeLa Cells; D015801:Helminth Proteins / Q000378:metabolism*; D006801:Humans; D048369:MAP Kinase Kinase 1; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D018631:ras Proteins / Q000378:metabolism; D000096985:Calponins
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D002352:Carrier Proteins; D004815:Epidermal Growth Factor; D015801:Helminth Proteins; D048369:MAP Kinase Kinase 1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D020928:Mitogen-Activated Protein Kinases; D009124:Muscle Proteins; D017346:Protein Serine-Threonine Kinases; D018631:ras Proteins; C485425:LAMTOR3 protein, human; C118619:calponin homolog protein, Schistosoma japonicum; D000096985:Calponins; C482125:MAP2K1 protein, human; C482127:Map2k1 protein, mouse