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.
Formstecher
E
E
INSERM U114, Collège de France, Paris.
Ramos
J W
JW
Fauquet
M
M
Calderwood
D A
DA
Hsieh
J C
JC
Canton
B
B
Nguyen
X T
XT
Barnier
J V
JV
Camonis
J
J
Ginsberg
M H
MH
Chneiweiss
H
H
D016475:3T3 Cells; D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D051017:Apoptosis Regulatory Proteins; D015152:Blotting, Northern; D016466:CHO Cells; D002455:Cell Division; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival; D006224:Cricetinae; D003593:Cytoplasm / Q000378:metabolism*; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D008164:Luminescent Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008856:Microscopy, Fluorescence; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D011233:Precipitin Tests; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014158:Transcription, Genetic; D014162:Transfection; D020798:Two-Hybrid System Techniques
D051017:Apoptosis Regulatory Proteins; D018076:DNA, Complementary; D008164:Luminescent Proteins; C490444:Pea15 protein, mouse; D010750:Phosphoproteins; D049452:Green Fluorescent Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases