In vivo nuclear Ca2+-ATPase phosphorylation triggers intermediate size molecular transport to the nucleus.

Outer nuclear membrane is endowed with a SERCA type Ca2+-ATPase which pumps calcium into the nuclear envelope lumen and creates calcium stores. Variation in this calcium pool, among other things, regulates nuclear transport. The transport of Nuclear Localization Signal (NLS)-containing molecules into the nucleus is well established. Intermediate size molecules lacking an NLS translocate to the nucleus and its mechanism remains obscure. It is observed here that the treatment of HEK 293 cells in culture with dibutyryl cyclic AMP (db-cAMP) or forskolin (FK) triggered transport of Calcium Green 10kDa dextran into the nucleus. Under similar conditions Fluo-3-AM accumulated around the nuclei. cAMP-dependent protein kinase phosphorylated 105kDa nuclear Ca2+-ATPase (NCA) which served as a trigger for NLS-independent transport into the nucleus.