Luise M, Presotto C, Senter L, Betto R, Ceoldo S, Furlan S, Salvatori S, Sabbadini R A, Salviati G
Centro di Studio per la Biologia e la Fisiopatologia Muscolare-Dipartimento di Scienze Biomediche Sperimentali, Universita' di Padova, Italy.
Biochem J. 1993 Jul 1;293 ( Pt 1)(Pt 1):243-7. doi: 10.1042/bj2930243.
Dystrophin, the protein coded by the gene missing in Duchenne muscular dystrophy, is assumed to be a component of the membrane cytoskeleton of skeletal muscle. Like other cytoskeletal proteins in different cell types, dystrophin bound to sarcolemma membranes was found to be phosphorylated by endogenous protein kinases. The phosphorylation of dystrophin was activated by cyclic AMP, cyclic GMP, calcium and calmodulin, and was inhibited by cyclic AMP-dependent protein kinase peptide inhibitor, mastoparan and heparin. These results suggest that membrane-bound dystrophin is a substrate of endogenous cyclic AMP- and cyclic GMP-dependent protein kinases, calcium/calmodulin-dependent kinase and casein kinase II. The possibility that dystrophin could be phosphorylated by protein kinase C is suggested by the inhibition of phosphorylation by staurosporin. On the other hand dystrophin seems not to be a substrate for protein tyrosine kinases, as shown by the lack of reaction of phosphorylated dystrophin with a monoclonal antiphosphotyrosine antibody. Sequence analysis indicates that dystrophin contains seven potential phosphorylation sites for cyclic AMP- and cyclic GMP-dependent protein kinases (all localized in the central rod domain of the molecule) as well as several sites for protein kinase C and casein kinase II. Interestingly, potential sites of phosphorylation by protein kinase C and casein kinase II are located in the proximity of the actin-binding site. These results suggest, by analogy with what has been demonstrated in the case of other cytoskeletal proteins, that the phosphorylation of dystrophin by endogenous protein kinases may modulate both self assembly and interaction of dystrophin with other cytoskeletal proteins in vivo.
肌营养不良蛋白是杜氏肌营养不良症中缺失基因所编码的蛋白质，被认为是骨骼肌膜细胞骨架的一个组成部分。与不同细胞类型中的其他细胞骨架蛋白一样，发现与肌膜结合的肌营养不良蛋白可被内源性蛋白激酶磷酸化。肌营养不良蛋白的磷酸化被环磷酸腺苷（cAMP）、环磷酸鸟苷（cGMP）、钙和钙调蛋白激活，并被环磷酸腺苷依赖性蛋白激酶肽抑制剂、蜂毒素和肝素抑制。这些结果表明，膜结合的肌营养不良蛋白是内源性环磷酸腺苷依赖性和环磷酸鸟苷依赖性蛋白激酶、钙/钙调蛋白依赖性激酶和酪蛋白激酶II的底物。星形孢菌素对磷酸化的抑制表明肌营养不良蛋白可能被蛋白激酶C磷酸化。另一方面，磷酸化的肌营养不良蛋白与单克隆抗磷酸酪氨酸抗体缺乏反应，表明肌营养不良蛋白似乎不是蛋白酪氨酸激酶的底物。序列分析表明，肌营养不良蛋白含有七个环磷酸腺苷依赖性和环磷酸鸟苷依赖性蛋白激酶的潜在磷酸化位点（均位于分子的中央杆状结构域）以及几个蛋白激酶C和酪蛋白激酶II的位点。有趣的是，蛋白激酶C和酪蛋白激酶II的潜在磷酸化位点位于肌动蛋白结合位点附近。这些结果通过与其他细胞骨架蛋白的情况进行类比表明，内源性蛋白激酶对肌营养不良蛋白的磷酸化可能在体内调节肌营养不良蛋白的自我组装及其与其他细胞骨架蛋白的相互作用。
