ERK dimers and scaffold proteins: unexpected partners for a forgotten (cytoplasmic) task.
Signals transmitted by ERK1/2 MAP Kinases regulate the functions of multiple substrates present in the nucleus and in the cytoplasm, in similar proportions. In spite of this fact, the prevailing trend of the field has been to focus on the nuclear component, being considered the main executor of ERK biological functions. Following this fashion, scaffold proteins have been often described as modulators of ERK phosphorylation in their route, either as monomers or as dimers, to their ultimate destination at the nucleus. Contrarily, recent findings demonstrate that scaffolds and ERK dimers are essential for the activation of cytoplasmic but not nuclear substrates. Dimerization is critical for connecting the scaffolded ERK complex to cognate cytoplasmic substrates, while nuclear substrates are activated by ERK monomers. Furthermore, blocking ERK cytoplasmic signals by preventing ERK dimerization, is sufficient for attenuating cellular proliferation, transformation and tumor development. These new results highlight the importance of ERK cytoplasmic signals, disclose an unprecedented functional relationship between scaffold proteins and ERK dimers and identify dimerization as a key determinant of the spatial specificity of ERK signals.
Casar
Berta
B
Instituto de Biomedicina y Biotecnología de Cantabria, Consejo Superior de Investigaciones Científicas -IDICAN-Universidad de Cantabria, Departamento de Biología Molecular, Facultad de Medicina, Santander, Cantabria, Spain.
Pinto
Adán
A
Crespo
Piero
P
D000818:Animals; D002477:Cells / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D034521:Nuclear Matrix-Associated Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D055503:Protein Multimerization; D015398:Signal Transduction
D034521:Nuclear Matrix-Associated Proteins; D048049:Extracellular Signal-Regulated MAP Kinases