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.

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  • Additional Information
    • Source:
      Publisher: Wiley on behalf of the International Society for Neurochemistry Country of Publication: England NLM ID: 2985190R Publication Model: Print Cited Medium: Print ISSN: 0022-3042 (Print) Linking ISSN: 00223042 NLM ISO Abbreviation: J Neurochem Subsets: MEDLINE
    • Publication Information:
      Publication: 2001- : Oxford, UK : Wiley on behalf of the International Society for Neurochemistry
      Original Publication: New York : Raven Press
    • Subject Terms:
      Calmodulin-Binding Proteins/*genetics ; Calmodulin-Binding Proteins/*metabolism ; Chromosomal Proteins, Non-Histone/*metabolism ; High Mobility Group Proteins/*metabolism ; Isoenzymes/*genetics ; Isoenzymes/*metabolism ; Nerve Tissue Proteins/*genetics ; Nerve Tissue Proteins/*metabolism ; Promoter Regions, Genetic/*physiology ; Protein Kinase C/*genetics ; Protein Kinase C/*metabolism; Animals ; Binding, Competitive ; CDC2 Protein Kinase/physiology ; DNA/metabolism ; Neurogranin ; Phosphorylation ; Rats
    • Abstract:
      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.
    • Accession Number:
      0 (Calmodulin-Binding Proteins)
      0 (Chromosomal Proteins, Non-Histone)
      0 (High Mobility Group Proteins)
      0 (Isoenzymes)
      0 (Nerve Tissue Proteins)
      0 (Nrgn protein, rat)
      132654-77-4 (Neurogranin)
      9007-49-2 (DNA)
      EC 2.7.1.- (protein kinase C gamma)
      EC 2.7.11.13 (Protein Kinase C)
      EC 2.7.11.22 (CDC2 Protein Kinase)
    • Publication Date:
      Date Created: 20000105 Date Completed: 20000118 Latest Revision: 20190630
    • Publication Date:
      20231215
    • Accession Number:
      10.1046/j.1471-4159.2000.0740392.x
    • Accession Number:
      10617144