Protein kinase G type II is required for night-to-day progression of the mammalian circadian clock.
Circadian clocks comprise a cyclic series of dynamic cellular states, characterized by the changing availability of substrates that alter clock time when activated. To determine whether circadian clocks, like the cell cycle, exhibit regulation by key phosphorylation events, we examined endogenous kinase regulation of timekeeping in the mammalian suprachiasmatic nucleus (SCN). Short-term inhibition of PKG-II but not PKG-Ibeta using antisense oligodeoxynucleotides delayed rhythms of electrical activity and Bmal1 mRNA. Phase resetting was rapid and dynamic; inhibition of PKG-II forced repetition of the last 3.5 hr of the cycle. Chronic inhibition of PKG-II disrupted electrical activity rhythms and tonically increased Bmal1 mRNA. PKG-II-like immunoreactivity was detected after coimmunoprecipitation with CLOCK, and CLOCK was phosphorylated in the presence of active PKG-II. PKG-II activation may define a critical control point for temporal progression into the daytime domain by acting on the positive arm of the transcriptional/translational feedback loop.
Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, B107 CLSL, 601 South Goodwin Avenue, Urbana, Illinois 61801, USA.
Shelley A
SA
Tischkau
Jennifer W
JW
Mitchell
Laura A
LA
Pace
Jessica W
JW
Barnes
Jeffrey A
JA
Barnes
Martha U
MU
Gillette
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D041681:NIH 3T3 Cells; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D017869:Cyclic GMP-Dependent Protein Kinases