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Regulation of anchoring of the RII regulatory subunit of PKA to AKAP95 by threonine phosphorylation of RII: implications for chromosome dynamics at mitosis

¹ Institute of Medical Biochemistry, Faculty of Medicine, University of Oslo, PO Box 1112 Blindern, 0317 Oslo, Norway
² Ruhr Universität Bochum, Institut für Physiologische Chemie, MA2 Nord Raum 40, 44780 Bochum, Germany

*Author for correspondence (e-mail: philippe.collas{at}basalmed.uio.no)

Accepted June 10, 2001

CDK1 phosphorylates the A-kinase regulatory subunit RII on threonine 54 (T54) at mitosis, an event proposed to alter the subcellular localization of RII. Using an RII-deficient leukemic cell line (Reh) and stably transfected Reh cell clones expressing wild-type RII or an RII(T54E) mutant, we show that RII associates with chromatin-bound A-kinase anchoring protein AKAP95 at mitosis and that this interaction involves phosphorylation of RII on T54. During interphase, both RII and RII(T54E) exhibit a centrosome-Golgi localization, whereas AKAP95 is intranuclear. At mitosis and in a mitotic extract, most RII, but not RII(T54E), co-fractionates with chromatin, onto which it associates with AKAP95. This correlates with T54 phosphorylation of RII. Disrupting AKAP95-RII anchoring or depleting RII from the mitotic extract promotes premature chromatin decondensation. In a nuclear reconstitution assay that mimics mitotic nuclear reformation, RII is threonine dephosphorylated and dissociates from AKAP95 prior to assembly of nuclear membranes. Lastly, the Reh cell line exhibits premature chromatin decondensation in vitro, which can be rescued by addition of wild-type RII or an RII(T54D) mutant, but not RII(T54E, A, L or V) mutants. Our results suggest that CDK1-mediated T54 phosphorylation of RII constitutes a molecular switch controlling anchoring of RII to chromatin-bound AKAP95, where the PKA-AKAP95 complex participates in remodeling chromatin during mitosis.

Key words: Mitosis, Chromosome Condensation, Phosphorylation, PKA, AKAP95

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