Tesis doctoral de Paloma Goñi Oliver
Gsk-3 activity can be regulated by phosphorylation and through interaction with gsk-3-binding proteins; here we describe n-terminal proteolysis as a novel way to regulate gsk-3. Gsk-3¿ and gsk-3íY were truncated by calpain, generating two fragments of 40 and 30 kda, a proteolytic process that was inhibited by specific calpain inhibitors. The 30 kda fragment was originated by cleavage of the 49asp – 50arg peptide bound. These truncated isoforms were active kinases. We also found that lithium, a gsk-3 inhibitor, inhibits full-length and cleaved gsk-3 isoforms with the same ic50 value. When cultured cortical neurons were exposed with ionomycin, glutamate, or nmda, gsk-3 was truncated. This truncation was blocked by the calpain inhibitor calpeptin, at the same concentration at which it inhibits calpain-mediated cleavage of other well-known calpain substrates. Truncated gsk-3 forms did not accumulate, suggesting that a short-lived product is formed. Gsk-3 truncation mediated by calpain prevents its binding to 14-3-3¿. In addition, overexpression of the truncated gsk-3 form ([50-420]-gsk-3íY) in cos-7 cells showed that the n-terminal is involved in nuclear import, since the truncated form is only present in the cytoplasm.
Datos académicos de la tesis doctoral «Truncacion de gsk-3 por calpaina: implicaciones fisiologicas y patologicas«
- Título de la tesis: Truncacion de gsk-3 por calpaina: implicaciones fisiologicas y patologicas
- Autor: Paloma Goñi Oliver
- Universidad: Autónoma de Madrid
- Fecha de lectura de la tesis: 17/06/2009
Dirección y tribunal
- Director de la tesis
- Felix Hernandez Perez
- Tribunal
- Presidente del tribunal: cecilio Gimenez martin
- Miguel Medina padilla (vocal)
- pilar Gomez ramos (vocal)
- teresa Iglesias vacas (vocal)
