Phosphorylated KDR can be located in the nucleus of neoplastic cells.
KDR (kinase insert domain receptor) phosphorylation induces several effects which lead eventually to cell proliferation and survival. The precise mechanisms by which KDR, once it is activated, communicates with the nucleus are starting to be understood but have not yet been completely unravelled. Two in vitro studies on animal cell lines reported in the literature have demonstrated that, following stimulation with VEGF, KDR is actually translocated within the nucleus. Our aim was to investigate whether this translocation occurs in human cells both in vitro and in vivo. Using laser scanning confocal microscopy, a variable nuclear localization of phosphorylated and total KDR in cell lines and tumour samples was found. In human neoplastic cell lines, hypoxic stimulation greatly increased the nuclear amount of total KDR but less so that of the phosphorylated form. Only after hypoxia and VEGF stimulation there was a comparably increased expression of phosphorylated and total KDR observed in the nuclei of these cells. We conclude that neoplastic cells show a variable expression of total and phosphorylated KDR in the nucleus. The precise functional meaning of nuclear location remains to be established.
Departamento de Bioquimica y Biologia Molecular I, Facultad de Biologia, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid 28040, Espania, Spain.
Cristina
C
Blazquez
Nathan
N
Cook
Kingsley
K
Micklem
Adrian L
AL
Harris
Kevin C
KC
Gatter
Francesco
F
Pezzella
D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D018613:Microscopy, Confocal; D009369:Neoplasms / Q000378:metabolism* / Q000648:ultrastructure; D010766:Phosphorylation; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D040301:Vascular Endothelial Growth Factor Receptor-2