Structure and function of myotonin protein kinase causing myotonic dystrophy and analysis of its pathological aspects

引起强直性肌营养不良的肌强直蛋白激酶的结构和功能及其病理学分析

• 批准号: 08670178
• 负责人: HASHIMOTO Eikichi
• 金额: $ 1.22万
• 依托单位: Tottori University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670178/
• 关键词: Myotonic dystrophy; Myotonin protein kinase; Hl histone kinase; Protein kinase; Protein phosphorylation; Signal transduction; Genetic disease; Hlヒストンキナーゼ

1. An Hl histone kinase has been partially purified from rabbit skeletal muscle through sequential column chromatographies on DEAE-Sephacel, Hl histone-Sepharose and hydroxylapatite.2. The molecular mass of the Hl histone kinase was estimated to be approximately 45-50 kDa by the gel filtration and in-gel assay methods.3. The Hl histone kinase activity was not seriously influenced by the addition of cAMP,Ca^<2+> and phospholipid or calmodulin which were known as activators of several second messenger-dependent protein kinases, or by the addition of protein kinase A inhibitor peptide and heparin known as the inhibitor of casein kinase II.But, the activity was moderately inhibited by protein kinase C inhibitor peptide.4. Substrate specificity of the Hl histone kinase was similar to that of protein kinase C,however different from those of protein kinase A,cdc2 kinase and casein kinases.5. The Hl histone kinase phosphorylated serine residue (s) at the carboxyl-terminal portion of this histone obtained by bisecting it with N-bromosuccinimide as well as protein kinase C.6. The properties of this Hl histone kinase were similar with, but not exactly same as those of the catalytic fragment of protein kinase C.The relation between the Hl histone kinase obtained in this study and the protein serine/threonine kinase, which might be involved in causing myotonic dystrophy, or protein kinase C has been remained to be studied.

1。HL组蛋白激酶已通过Deae-Sephacel，HL组蛋白 - 塞帕罗斯和羟基磷灰石的顺序色谱柱的顺序色谱仪从兔骨骼肌部分纯化。2。通过凝胶过滤和凝胶测定方法，估计HL组蛋白激酶的分子质量约为45-50kDa。3。 HL组蛋白激酶的活性不受添加CAMC，Ca^<2+>和磷脂或钙调蛋白的添加严重影响，这些激活剂被称为几种依赖于Messenger依赖性蛋白激酶的激活剂，或者通过添加蛋白激酶A抑制剂肽和肝素的抑制剂II的抑制剂II的抑制剂II。肽4。 HL组蛋白激酶的底物特异性与蛋白激酶C的底物特异性相似，但是与蛋白激酶A，CDC2激酶和酪蛋白激酶的底物特异性不同。5。通过将其与N-溴糖酰亚胺与蛋白激酶C.6分成偶联的HL组蛋白激酶磷酸化的丝氨酸残基（S）在该组蛋白的羧基末端部分处。该HL组蛋白激酶的特性与蛋白激酶的催化片段相似，但并不完全相同。在这项研究中获得的HL组蛋白激酶与蛋白质丝氨酸/苏氨酸激酶之间的关系可能与导致肌动型性增生症或蛋白激酶C的蛋白丝氨酸/苏氨酸激酶有关。

项目成果

Kubota, Norika: "Studies on a Ca^<2+>-and cyclic nucleotide-independent Hl histone kinase purified from rabbit skeletal muscle." Yonago Acta medica. 41. 31-44 (1998)

Kubota, Norika：“对从兔骨骼肌中纯化的不依赖于 Ca^2 和环核苷酸的 H1 组蛋白激酶的研究。”

Liu,Ying: "Studies on the phosphorylation of a Mr 25,000 protein,a putative protein phosphatase 2A modulator,by casein kinase I,and analysis of multiple endogenrus phosphatas" J.Biochem.119(5). 1004-1013 (1996)

刘英：“酪蛋白激酶 I 对 Mr 25,000 蛋白（一种推定的蛋白磷酸酶 2A 调节剂）磷酸化的研究，以及多种内源磷酸酶的分析”J.Biochem.119(5)。

Hashimoto,Eikichi: "Phosphonylated sites of Mr 25,000 protein,a putative protein phosphatase 2A modulath and phosphonylation of the synthetic poptide conteining these sity by protein kinase C" J.Biochem.119(4). 626-632 (1996)

Hashimoto, Eikichi：“Mr 25,000 蛋白的磷酸化位点，一种推定的蛋白磷酸酶 2A 调节剂，以及通过蛋白激酶 C 对包含这些位点的合成肽进行磷酸化”J.Biochem.119(4)。

Hashimoto, Eikichi: "Phosphorylated sites of M_r 25,000 protein, a putative protein phoaphatase 2A modulator, and phosphorylation of the synthetic peptide containing these sites by protein kinase C." J.Biochem.119. 626-632 (1996)

Hashimoto, Eikichi：“M_r 25,000 蛋白（一种推定的蛋白磷酸酶 2A 调节剂）的磷酸化位点，以及含有这些位点的合成肽被蛋白激酶 C 磷酸化。”

Liu, Ying: "Studies on the phosphorylation of a M_r 25,000 proteinm, a putative protein phosphatase 2A modular, by casein kinase I,and analysis of multiple endogenous phosphates." J.Biochem.119. 1004-1013 (1996)

Liu, Ying：“研究酪蛋白激酶 I 对 M_r 25,000 蛋白（一种假定的蛋白磷酸酶 2A 模块）的磷酸化，以及多种内源磷酸盐的分析。”