title: Phosphoinositide-3-kinases p110α and p110β mediate S phase entry in astroglial cells in the marginal zone of rat neocortex.
abstract: In cells cultured from neocortex of newborn rats, phosphoinositide-3-kinases of class I regulate the DNA synthesis in a subgroup of astroglial cells. We have studied the location of these cells as well as the kinase isoforms which facilitate the S phase entry. Using dominant negative (dn) isoforms as well as selective pharmacological inhibitors we quantified S phase entry by nuclear labeling with bromodeoxyuridine (BrdU). Only in astroglial cells harvested from the marginal zone (MZ) of the neocortex inhibition of phosphoinositide-3-kinases reduced the nuclear labeling with BrdU, indicating that neocortical astroglial cells differ in the regulation of proliferation. The two kinase isoforms p110α and p110β were essential for S phase entry. p110α diminished the level of the p27(Kip1) which inactivates the complex of cyclin E and CDK2 necessary for entry into the S phase. p110β phosphorylated and inhibited glycogen synthase kinase-3β which can prevent S-phase entry. Taken together, both isoforms mediated S phase in a subgroup of neocortical astroglial cells and acted via distinct pathways.
authors.affiliation: Institute of Experimental and Clinical Pharmacology und Toxicology, Albert-Ludwigs-University Freiburg Freiburg, Germany.
authors.forename: Rabea
authors.initials: R
authors.lastname: Müller
authors.forename: Catharina
authors.initials: C
authors.lastname: Fischer
authors.forename: Thomas
authors.initials: T
authors.lastname: Wilmes
authors.forename: Bernd
authors.initials: B
authors.lastname: Heimrich
authors.forename: Vanessa
authors.initials: V
authors.lastname: Distel
authors.forename: Norbert
authors.initials: N
authors.lastname: Klugbauer
authors.forename: Dieter K
authors.initials: DK
authors.lastname: Meyer
keywords: bromodeoxyuridine; glycogen synthase kinase-3β; marginal zone; p110α; p110β; p27Kip1; rat neocortex