Previous studies showed that prostaglandin F2α (PGF 2α) stimulated fibroblast growth factor-2 (FGF-2) and fibroblast growth factor receptor 2 (FGFR2) cytosolic and nuclear accumulation, however, the endocytic pathway has not been elucidated. This study demonstrates that although PGF2α, increased the formation of clathrin-coated structures in Py1a rat osteoblasts, they were not involved in FGF-2 and FGFR2 trafficking. PGF2α, increased binding of FGF-2 and FGFR2 and co-localization of reactive sites in addition to nuclear translocation at the nuclear pore complex level. FGF-2 and FGFR2 were in close spatial correlation with importin β, further supporting nuclear import of the FGF-2/FGFR2 complex, Immunogold and immunofluorescence techniques as well as Western blotting demonstrated increased importin β protein labeling in response to PGF2α. Similar to PGF2α, phorbol 12-myristate 13-acetate (PMA) also increased importin β protein. These data strongly suggest that prostaglandins may regulate osteoblast metabolism via FGF-2/FGFR2/importin β nuclear trafficking.
PGF2alpha increases FGF-2 and FGFR2 trafficking in Py1a rat osteoblasts via clathrin independent and importin beta dependent pathway
MARCHETTI, Luigi;SABBIETI, Maria Giovanna;AGAS, DIMITRIOS;
2006-01-01
Abstract
Previous studies showed that prostaglandin F2α (PGF 2α) stimulated fibroblast growth factor-2 (FGF-2) and fibroblast growth factor receptor 2 (FGFR2) cytosolic and nuclear accumulation, however, the endocytic pathway has not been elucidated. This study demonstrates that although PGF2α, increased the formation of clathrin-coated structures in Py1a rat osteoblasts, they were not involved in FGF-2 and FGFR2 trafficking. PGF2α, increased binding of FGF-2 and FGFR2 and co-localization of reactive sites in addition to nuclear translocation at the nuclear pore complex level. FGF-2 and FGFR2 were in close spatial correlation with importin β, further supporting nuclear import of the FGF-2/FGFR2 complex, Immunogold and immunofluorescence techniques as well as Western blotting demonstrated increased importin β protein labeling in response to PGF2α. Similar to PGF2α, phorbol 12-myristate 13-acetate (PMA) also increased importin β protein. These data strongly suggest that prostaglandins may regulate osteoblast metabolism via FGF-2/FGFR2/importin β nuclear trafficking.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.