LIPID SIGNALLING IN THE CELL NUCLEUS

Project: Research project

Project Details

Description

The U.S. PI has a long-standing interest in the various aspects of protein
kinase C (PKC) isozyme signaling within cells. The PI has previously
investigated in detail one particular pKC isozyme, PKC B2, and has generated a
considerable amount of knowledge regarding the mechanisms surrounding
activation of this isozyme. The present parent project for this FIRCA
application by the PI has now shifted to explore the functional
characterization of an atypical PKC isozyme, PKCi, in human leukemia cell
survival. In examining factors responsible for the nuclear activation of PKC B2
prior to mitosis, the PI's laboratory isolated a nuclear PI-PLC from G2 phase
nuclei. Preliminary experiments using antibodies to known PI-PLC isozymes
indicated that this nuclear PI-PLC did not correspond to any of the previously
identified PI-PLC isozymes. The foreign collaborator, while working with
regenerating rat hepatocytes, also observed the presence of a novel nuclear
PI-PLC activity involved in cell cycle regulation. Given these common findings
and interests, and given the foreign collaborator's expertise in the
biochemical analysis of phosphatidylinositol-metabolizing enzymes, a new
collaborative effort has arisen between these investigators. Therefore, the
main thrust of this proposal is to identify this novel nuclear PI-PLC activity.

In addition, recent data suggests that a phosphatidylinositol 3-kinase (PI3K)
signaling system exists within the nucleus and that this nuclear PI3K signaling
system is distinct from the well described cytoplasmic-cell membrane PI3K
system. The novel nuclear PI3K pathway is responsible for PKB activation. These
preliminary results suggest that PI3K and PKB activation may play a direct
physiologic role in nuclear events associated with cellular proliferation and
cell cycle progression. The second and third specific aims therefore propose to
expand and confirm these preliminary results of the roles of nuclear PI3K and
PKB in these cellular events.
StatusNot started