PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase.

Etienne Formstecher (1) , Joe W. Ramos (2) , Mireille Fauquet (1) , David A. Calderwood (2) , Jyh-Cheng Hsieh (2) , Brigitte Canton (1) , Xuan-Thao Nguyen (2) , Jean-Vianney Barnier (3) , Jacques H. Camonis (4) , Mark H. Ginsberg (2) , Hervé Chneiweiss (1)

1 INSERM U114 - Collège de France - Chaire Neuropharmacologie
2 Department of Vascular Biology
3 INAF - Institut de Neurobiologie Alfred Fessard
4 Transduction du signal et oncogénèse

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.

Domaines: Neurosciences [q-bio.NC]

Etienne Formstecher, Joe W. Ramos, Mireille Fauquet, David A. Calderwood, Jyh-Cheng Hsieh, et al.. PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase.. Developmental Cell, 2001, 1 (2), pp.239-50. ⟨10.1016/S1534-5807(01)00035-1⟩. ⟨hal-00122265⟩