Localization of the MP1-MAPK scaffold complex to endosomes is mediated by p14 and required for signal transduction

Dev Cell. 2002 Dec;3(6):803-14. doi: 10.1016/s1534-5807(02)00364-7.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing*
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Carrier Proteins / metabolism*
  • Cell Membrane / metabolism
  • Endosomes / drug effects
  • Endosomes / metabolism*
  • Epidermal Growth Factor / metabolism
  • Epidermal Growth Factor / pharmacology
  • Eukaryotic Cells / cytology
  • Eukaryotic Cells / metabolism*
  • HeLa Cells
  • Helminth Proteins / metabolism*
  • Humans
  • MAP Kinase Kinase 1
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / physiology*
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Mitogen-Activated Protein Kinases / metabolism*
  • Muscle Proteins / metabolism*
  • Protein Transport / physiology*
  • Protein-Serine-Threonine Kinases / metabolism
  • Up-Regulation / drug effects
  • Up-Regulation / physiology
  • ras Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Adaptor Proteins, Vesicular Transport
  • Carrier Proteins
  • Helminth Proteins
  • LAMTOR3 protein, human
  • Muscle Proteins
  • calponin homolog protein, Schistosoma japonicum
  • Epidermal Growth Factor
  • Protein-Serine-Threonine Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human
  • Map2k1 protein, mouse
  • Mitogen-Activated Protein Kinase Kinases
  • ras Proteins