PMID- 10500146
OWN - NLM
STAT- MEDLINE
DCOM- 19991021
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 20
DP  - 1999 Sep 28
TI  - Regulation of cyclin-dependent kinase 5 catalytic activity by phosphorylation.
PG  - 11156-60
AB  - Cyclin-dependent kinase 5 (cdk5) is found in an active form only in neuronal
      cells. Activation by virtue of association with the cyclin-like neuronal proteins
      p35 (or its truncated form p25) and p39 is the only mechanism currently shown to 
      regulate cdk5 catalytic activity. In addition to cyclin binding, other members of
      the cdk family require for maximal activation phosphorylation of a Ser/Thr
      residue (Thr(160) in the case of cdk-2) that is conserved in all cdks except
      cdk8. This site is phosphorylated by cdk-activating kinases, which, however, do
      not phosphorylate cdk5. To examine the possible existence of a
      phosphorylation-dependent regulatory mechanism in the case of cdk5, we have
      metabolically labeled PC12 cells with (32)P(i) and shown that the endogenous cdk5
      is phosphorylated. Bacterially expressed cdk5 also can be phosphorylated by PC12 
      cell lysates. Phosphorylation of cdk5 by a PC12 cell lysate results in a
      significant increase in cdk5/p25 catalytic activity. Ser(159) in cdk5 is
      homologous to the regulatory Thr(160) in cdk2. A Ser(159)-to-Ala (S159A) cdk5
      mutant did not show similar activation, which suggests that cdk5 is also
      regulated by phosphorylation at this site. Like other members of the cdk family, 
      cdk5 catalytic activity is influenced by both p25 binding and phosphorylation. We
      show that the cdk5-activating kinase (cdk5AK) is distinct from the cdk-activating
      kinase (cyclin H/cdk7) that was reported previously to neither phosphorylate cdk5
      nor affect its activity. We also show that casein kinase I, but not casein kinase
      II, can phosphorylate and activate cdk5 in vitro.
FAU - Sharma, P
AU  - Sharma P
AD  - Laboratory of Neurochemistry, National Institute of Neurological Diseases and
      Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
FAU - Sharma, M
AU  - Sharma M
FAU - Amin, N D
AU  - Amin ND
FAU - Albers, R W
AU  - Albers RW
FAU - Pant, H C
AU  - Pant HC
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Casein Kinases)
RN  - EC 2.7.11.1 (Cyclin-Dependent Kinase 5)
RN  - EC 2.7.11.22 (Cdk5 protein, rat)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Casein Kinases
MH  - Catalysis
MH  - Cyclin-Dependent Kinase 5
MH  - Cyclin-Dependent Kinases/*metabolism
MH  - Enzyme Activation
MH  - Molecular Sequence Data
MH  - PC12 Cells
MH  - Phosphorylation
MH  - Protein Kinases/metabolism
MH  - Rats
PMC - PMC18003
EDAT- 1999/09/29 00:00
MHDA- 1999/09/29 00:01
CRDT- 1999/09/29 00:00
PHST- 1999/09/29 00:00 [pubmed]
PHST- 1999/09/29 00:01 [medline]
PHST- 1999/09/29 00:00 [entrez]
AID - 10.1073/pnas.96.20.11156 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Sep 28;96(20):11156-60. doi:
      10.1073/pnas.96.20.11156.