PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase.
The ERK 1/2 MAP kinase pathway controls cell growth and survival and modulates integrin function. Here, we report that PEA-15, a protein variably expressed in multiple cell types, blocks ERK-dependent transcription and proliferation by binding ERKs and preventing their localization in the nucleus. PEA-15 contains a nuclear export sequence required ... for its capacity to anchor ERK in the cytoplasm. Genetic deletion of PEA-15 results in increased ERK nuclear localization with consequent increased cFos transcription and cell proliferation. Thus, PEA-15 can redirect the biological outcome of MAP kinase signaling by regulating the subcellular localization of ERK MAP kinase.
Mesh Terms:
3T3 Cells, Active Transport, Cell Nucleus, Amino Acid Sequence, Animals, Blotting, Northern, CHO Cells, Cell Division, Cell Nucleus, Cell Survival, Cricetinae, Cytoplasm, DNA, Complementary, Dose-Response Relationship, Drug, Green Fluorescent Proteins, Immunohistochemistry, Luminescent Proteins, MAP Kinase Signaling System, Mice, Microscopy, Fluorescence, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, Models, Biological, Molecular Sequence Data, Mutation, Phosphoproteins, Precipitin Tests, Protein Binding, Sequence Homology, Amino Acid, Time Factors, Transcription, Genetic, Transfection, Two-Hybrid System Techniques
3T3 Cells, Active Transport, Cell Nucleus, Amino Acid Sequence, Animals, Blotting, Northern, CHO Cells, Cell Division, Cell Nucleus, Cell Survival, Cricetinae, Cytoplasm, DNA, Complementary, Dose-Response Relationship, Drug, Green Fluorescent Proteins, Immunohistochemistry, Luminescent Proteins, MAP Kinase Signaling System, Mice, Microscopy, Fluorescence, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinase 3, Mitogen-Activated Protein Kinases, Models, Biological, Molecular Sequence Data, Mutation, Phosphoproteins, Precipitin Tests, Protein Binding, Sequence Homology, Amino Acid, Time Factors, Transcription, Genetic, Transfection, Two-Hybrid System Techniques
Dev. Cell
Date: Aug. 01, 2001
PubMed ID: 11702783
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