Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Active Transport, Cell Nucleus
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Amino Acid Sequence
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Animals
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Apoptosis Regulatory Proteins
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Blotting, Northern
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CHO Cells
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Cell Division
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Cell Nucleus / metabolism
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Cell Survival
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Cricetinae
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Cytoplasm / metabolism*
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DNA, Complementary / metabolism
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Dose-Response Relationship, Drug
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Green Fluorescent Proteins
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Immunohistochemistry
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Luminescent Proteins / metabolism
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MAP Kinase Signaling System*
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Mice
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Microscopy, Fluorescence
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / metabolism*
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Mitogen-Activated Protein Kinases / physiology*
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Models, Biological
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Molecular Sequence Data
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Mutation
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Phosphoproteins / genetics
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Phosphoproteins / metabolism*
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Phosphoproteins / physiology*
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Precipitin Tests
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Protein Binding
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Sequence Homology, Amino Acid
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Time Factors
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Transcription, Genetic
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Transfection
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Two-Hybrid System Techniques
Substances
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Apoptosis Regulatory Proteins
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DNA, Complementary
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Luminescent Proteins
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Pea15 protein, mouse
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Phosphoproteins
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Green Fluorescent Proteins
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases