PMID- 10617144
OWN - NLM
STAT- MEDLINE
DCOM- 20000118
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 74
IP  - 1
DP  - 2000 Jan
TI  - Phosphorylation of HMG-I by protein kinase C attenuates its binding affinity to
      the promoter regions of protein kinase C gamma and neurogranin/RC3 genes.
PG  - 392-9
AB  - A 20-kDa DNA-binding protein that binds the AT-rich sequences within the
      promoters of the brain-specific protein kinase C (PKC) gamma and neurogranin/RC3 
      genes has been characterized as chromosomal nonhistone high-mobility-group
      protein (HMG)-I. This protein is a substrate of PKC alpha, beta, gamma, and delta
      but is poorly phosphorylated by PKC epsilon and zeta. Two major (Ser44 and Ser64)
      and four minor phosphorylation sites have been identified. The extents of
      phosphorylation of Ser44 and Ser64 were 1:1, whereas those of the four minor
      sites all together were <30% of the major one. These PKC phosphorylation sites
      are distinct from those phosphorylated by cdc2 kinase, which phosphorylates Thr53
      and Thr78. Phosphorylation of HMG-I by PKC resulted in a reduction of DNA-binding
      affinity by 28-fold as compared with 12-fold caused by the phosphorylation with
      cdc2 kinase. HMG-I could be additively phosphorylated by cdc2 kinase and PKC, and
      the resulting doubly phosphorylated protein exhibited a >100-fold reduction in
      binding affinity. The two cdc2 kinase phosphorylation sites of HMG-I are adjacent
      to the N terminus of two of the three predicted DNA-binding domains. In
      comparison, one of the major PKC phosphorylation sites, Ser64, is adjacent to the
      C terminus of the second DNA-binding domain, whereas Ser44 is located within the 
      spanning region between the first and second DNA-binding domains. The current
      results suggest that phosphorylation of the mammalian HMG-I by PKC alone or in
      combination with cdc2 kinase provides an effective mechanism for the regulation
      of HMG-I function.
FAU - Xiao, D M
AU  - Xiao DM
AD  - Endocrinology and Reproduction Research Branch, National Institute of Child
      Health and Human Development, National Institutes of Health, Bethesda, Maryland
      20892-4510, USA.
FAU - Pak, J H
AU  - Pak JH
FAU - Wang, X
AU  - Wang X
FAU - Sato, T
AU  - Sato T
FAU - Huang, F L
AU  - Huang FL
FAU - Chen, H C
AU  - Chen HC
FAU - Huang, K P
AU  - Huang KP
LA  - eng
PT  - Journal Article
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Calmodulin-Binding Proteins)
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (High Mobility Group Proteins)
RN  - 0 (Isoenzymes)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Nrgn protein, rat)
RN  - 132654-77-4 (Neurogranin)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.1.- (protein kinase C gamma)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.22 (CDC2 Protein Kinase)
SB  - IM
MH  - Animals
MH  - Binding, Competitive
MH  - CDC2 Protein Kinase/physiology
MH  - Calmodulin-Binding Proteins/*genetics/*metabolism
MH  - Chromosomal Proteins, Non-Histone/*metabolism
MH  - DNA/metabolism
MH  - High Mobility Group Proteins/*metabolism
MH  - Isoenzymes/*genetics/*metabolism
MH  - Nerve Tissue Proteins/*genetics/*metabolism
MH  - Neurogranin
MH  - Phosphorylation
MH  - Promoter Regions, Genetic/*physiology
MH  - Protein Kinase C/*genetics/*metabolism
MH  - Rats
EDAT- 2000/01/05 00:00
MHDA- 2000/01/05 00:01
CRDT- 2000/01/05 00:00
PHST- 2000/01/05 00:00 [pubmed]
PHST- 2000/01/05 00:01 [medline]
PHST- 2000/01/05 00:00 [entrez]
AID - 10.1046/j.1471-4159.2000.0740392.x [doi]
PST - ppublish
SO  - J Neurochem. 2000 Jan;74(1):392-9. doi: 10.1046/j.1471-4159.2000.0740392.x.