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Phosphorylation of HMG‐I by Protein Kinase C Attenuates Its Binding Affinity to the Promoter Regions of Protein Kinase C γ and Neurogranin/RC3 Genes
Author(s) -
Xiao DianMo,
Pak Jhang Ho,
Wang Xiaoming,
Sato Takayuki,
Huang Freesia L.,
Chen HaoChia,
Huang KuoPing
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0740392.x
Subject(s) - protein kinase c , phosphorylation , cyclin dependent kinase 1 , neurogranin , cyclin dependent kinase 2 , map2k7 , biology , microbiology and biotechnology , protein phosphorylation , protein kinase a , biochemistry , phosphorylation cascade , kinase , gene , cell cycle
A 20‐kDa DNA‐binding protein that binds the AT‐rich sequences within the promoters of the brain‐specific protein kinase C (PKC) γ and neurogranin/RC3 genes has been characterized as chromosomal nonhistone high‐mobility‐group protein (HMG)‐I. This protein is a substrate of PKC α, β, γ, and δ but is poorly phosphorylated by PKC ε and ζ. Two major (Ser 44 and Ser 64 ) and four minor phosphorylation sites have been identified. The extents of phosphorylation of Ser 44 and Ser 64 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 Thr 53 and Thr 78 . 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, Ser 64 , is adjacent to the C terminus of the second DNA‐binding domain, whereas Ser 44 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.