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Vol. 9, Issue 12, 3547-3560, December 1998
and
*Department of Pharmacology, University of Wisconsin Medical
School, Madison, Wisconsin 53706; and
Phosphoinositide signal transduction pathways in nuclei use enzymes
that are indistinguishable from their cytosolic analogues. We
demonstrate that distinct phosphatidylinositol phosphate
kinases (PIPKs), the type I and type II isoforms, are concentrated in nuclei of mammalian cells. The cytosolic and nuclear PIPKs display comparable activities toward the substrates
phosphatidylinositol 4-phosphate and
phosphatidylinositol 3-phosphate. Indirect immunofluorescence revealed that these kinases were associated with distinct subnuclear domains, identified as "nuclear speckles," which also contained pre-mRNA processing factors. A pool of nuclear
phosphatidylinositol bisphosphate (PIP2), the
product of these kinases, was also detected at these same sites by
monoclonal antibody staining. The localization of PIPKs and
PIP2 to speckles is dynamic in that both PIPKs and PIP2 reorganize along with other speckle components upon
inhibition of mRNA transcription. Because PIPKs have roles in the
production of most phosphatidylinositol second messengers,
these findings demonstrate that phosphatidylinositol signaling
pathways are localized at nuclear speckles. Surprisingly, the PIPKs and
PIP2 are not associated with invaginations of the nuclear
envelope or any nuclear membrane structure. The putative absence of
membranes at these sites suggests novel mechanisms for the generation
of phosphoinositides within these structures.
Department of Inflammation
Research, Tokyo Metropolitan Institute of Medical Science, Tokyo
113, Japan
Corresponding author. E-mail
address: raanders{at}facstaff.wisc.edu.
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