PMID- 10523312
OWN - NLM
STAT- MEDLINE
DCOM- 19991206
LR  - 20081120
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 20
DP  - 1999 Oct 15
TI  - Mammalian homologues of the plant Tousled gene code for cell-cycle-regulated
      kinases with maximal activities linked to ongoing DNA replication.
PG  - 5691-702
AB  - The Tousled (TSL) gene of the plant Arabidopsis thaliana encodes a
      serine/threonine kinase that is essential for proper flower development. Here we 
      report the cloning and characterization of two human putative homologues of the
      Arabidopsis TSL gene, termed TLK1 and TLK2 (Tousled-like kinase). At the protein 
      level, the two human Tlks share 84% sequence similarity with each other and
      almost 50% with Arabidopsis Tsl. Furthermore, nuclear localization signals and
      predicted coiled-coil regions are conserved in the N-terminal domains of all
      three kinases. The mammalian Tlks share several functional properties with plant 
      Tsl, including a broad expression, a propensity to dimerize and
      autophosphorylate, and a preference for similar substrates. Most interestingly,
      human Tlks are cell-cycle-regulated enzymes, displaying maximal activities during
      S phase. Whereas protein levels are virtually constant throughout the cell cycle,
      both Tlks appear to be regulated by cell-cycle-dependent phosphorylation.
      Drug-induced inhibition of DNA replication causes a rapid loss of Tlk activity,
      indicating that Tlk function is tightly linked to ongoing DNA replication. These 
      findings provide the first biochemical clues as to the possible molecular
      functions of Tlks, a highly conserved family of kinases implicated in the
      development of multicellular organisms.
FAU - Sillje, H H
AU  - Sillje HH
AD  - Department of Molecular Biology, Sciences II, 30 quai Ernest-Ansermet, University
      of Geneva, CH-1211 Geneva 4, Switzerland.
FAU - Takahashi, K
AU  - Takahashi K
FAU - Tanaka, K
AU  - Tanaka K
FAU - Van Houwe, G
AU  - Van Houwe G
FAU - Nigg, E A
AU  - Nigg EA
LA  - eng
SI  - GENBANK/AF162666
SI  - GENBANK/AF162667
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (DNA Primers)
RN  - 0 (DNA, Complementary)
RN  - 0 (Recombinant Proteins)
RN  - EC 2.7.1.- (Tlk1 protein, mouse)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TLK1 protein, human)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Arabidopsis/*enzymology/*genetics
MH  - Base Sequence
MH  - Cell Cycle
MH  - Cell Nucleus/enzymology
MH  - DNA Damage
MH  - DNA Primers/genetics
MH  - DNA Replication
MH  - DNA, Complementary/genetics/isolation & purification
MH  - *Genes, Plant
MH  - HeLa Cells
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Protein-Serine-Threonine Kinases/*genetics/metabolism
MH  - Recombinant Proteins/genetics/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Species Specificity
PMC - PMC1171636
EDAT- 1999/10/16 00:00
MHDA- 1999/10/16 00:01
CRDT- 1999/10/16 00:00
PHST- 1999/10/16 00:00 [pubmed]
PHST- 1999/10/16 00:01 [medline]
PHST- 1999/10/16 00:00 [entrez]
AID - 10.1093/emboj/18.20.5691 [doi]
PST - ppublish
SO  - EMBO J. 1999 Oct 15;18(20):5691-702. doi: 10.1093/emboj/18.20.5691.