Turner R S, Raynor R L, Mazzei G J, Girard P R, Kuo J F
Proc Natl Acad Sci U S A. 1984 May;81(10):3143-7. doi: 10.1073/pnas.81.10.3143.
Ontogenetic changes in the protein phosphorylation/dephosphorylation systems in rat brain were investigated. It was found that the activity level of phospholipid-sensitive Ca2+-dependent protein kinase (PL-Ca-PK) in the particulate fraction of grey and white matter and the soluble fraction of grey matter increased rapidly and markedly after birth, reached the highest level at day 30, and declined slightly or remained unchanged thereafter. The enzyme level in the soluble fraction of white matter, in contrast, remained constant throughout the development and maturation of brain. Various ontogenetic changes in the substrate proteins for PL-Ca-PK were also noted. The levels of myelin basic protein and other substrates (notably the Mr 87,000, 58,000, 54,000, and 50,000 protein in grey matter) progressively increased during development, reaching the highest level at adulthood. The level of the Mr 66,000 protein from the particulate fraction of white and grey matter, on the other hand, increased rapidly after birth, reached a peak at day 18, and then declined to the initial neonatal level at the adult stage. The time scale for the increases in the levels of PL-Ca-PK and its many substrates paralleled that of brain development and maturation (synaptogenesis and myelinogenesis). The activity levels of phosphoprotein phosphatases (assayed using 32P-labeled myelin basic protein, histone, and protamine sulfate) were found to only slightly (up to 60%) increase or decrease in certain fractions from different brain regions during development, suggesting that phosphorylation, compared to dephosphorylation, may be more important in determining the phosphorylation state of cellular proteins.
研究了大鼠大脑中蛋白质磷酸化/去磷酸化系统的个体发育变化。发现灰质和白质颗粒部分以及灰质可溶性部分中磷脂敏感性钙依赖性蛋白激酶（PL-Ca-PK）的活性水平在出生后迅速显著增加，在第30天达到最高水平，此后略有下降或保持不变。相比之下，白质可溶性部分中的酶水平在大脑发育和成熟过程中保持恒定。还注意到PL-Ca-PK底物蛋白的各种个体发育变化。髓鞘碱性蛋白和其他底物（特别是灰质中分子量为87,000、58,000、54,000和50,000的蛋白质）的水平在发育过程中逐渐增加，在成年期达到最高水平。另一方面，白质和灰质颗粒部分中分子量为66,000的蛋白质水平在出生后迅速增加，在第18天达到峰值，然后在成年期降至新生儿初始水平。PL-Ca-PK及其许多底物水平增加的时间尺度与大脑发育和成熟（突触形成和髓鞘形成）的时间尺度平行。发现磷蛋白磷酸酶的活性水平（使用32P标记的髓鞘碱性蛋白、组蛋白和硫酸鱼精蛋白进行测定）在发育过程中仅在不同脑区的某些部分略有增加或减少（最多60%），这表明与去磷酸化相比，磷酸化在确定细胞蛋白质的磷酸化状态方面可能更重要。
