PMID- 10542239
OWN - NLM
STAT- MEDLINE
DCOM- 19991213
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 45
DP  - 1999 Nov 5
TI  - Identification of inhibitory autophosphorylation sites in casein kinase I
      epsilon.
PG  - 32063-70
AB  - Casein kinase I epsilon (CKIepsilon) is a widely expressed protein kinase
      implicated in the regulation of diverse cellular processes including DNA
      replication and repair, nuclear trafficking, and circadian rhythm. CKIepsilon and
      the closely related CKIdelta are regulated in part through autophosphorylation of
      their carboxyl-terminal extensions, resulting in down-regulation of enzyme
      activity. Treatment of CKIepsilon with any of several serine/threonine
      phosphatases causes a marked increase in kinase activity that is self-limited. To
      identify the sites of inhibitory autophosphorylation, a series of
      carboxyl-terminal deletion mutants was constructed by site-directed mutagenesis. 
      Truncations that eliminated specific phosphopeptides present in the wild-type
      kinase were used to guide construction of specific serine/threonine to alanine
      mutants. Amino acids Ser-323, Thr-325, Thr-334, Thr-337, Ser-368, Ser-405,
      Thr-407, and Ser-408 in the carboxyl-terminal tail of CKIepsilon were identified 
      as probable in vivo autophosphorylation sites. A recombinant CKIepsilon protein
      with serine and threonine to alanine mutations eliminating these
      autophosphorylation sites was 8-fold more active than wild-type CKIepsilon using 
      IkappaBalpha as a substrate. The identified autophosphorylation sites do not
      conform to CKI substrate motifs identified in peptide substrates.
FAU - Gietzen, K F
AU  - Gietzen KF
AD  - Division of Molecular Biology, Department of Oncological Sciences, Huntsman
      Cancer Institute, Salt Lake City, Utah 84132, USA.
FAU - Virshup, D M
AU  - Virshup DM
LA  - eng
GR  - CA42014/CA/NCI NIH HHS/United States
GR  - CA71074/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Casein Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Amino Acid Substitution
MH  - Binding Sites
MH  - Casein Kinases
MH  - Cell Line
MH  - Circadian Rhythm
MH  - Consensus Sequence
MH  - DNA Repair
MH  - DNA Replication
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Peptide Mapping
MH  - Phosphorylation
MH  - Protein Kinases/*chemistry/genetics
MH  - Sequence Homology, Amino Acid
EDAT- 1999/11/05 00:00
MHDA- 1999/11/05 00:01
CRDT- 1999/11/05 00:00
PHST- 1999/11/05 00:00 [pubmed]
PHST- 1999/11/05 00:01 [medline]
PHST- 1999/11/05 00:00 [entrez]
AID - 10.1074/jbc.274.45.32063 [doi]
AID - S0021-9258(19)51527-7 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 5;274(45):32063-70. doi: 10.1074/jbc.274.45.32063.