Michalak M, Fu S Y, Milner R E, Busaan J L, Hance J E
Department of Biochemistry, University of Alberta, Edmonton, Canada.
Biochem Cell Biol. 1996;74(4):431-7. doi: 10.1139/o96-047.
Dystrophin is a protein product of the gene responsible for Duchenne and Becker muscular dystrophy. The protein is localized to the inner surface of sarcolemma and is associated with a group of membrane (glyco)proteins. Dystrophin links cytoskeletal actins via the dystrophin-associated protein complex to extracellular matrix protein, laminin. This structural organization implicates the role of dystrophin in stabilizing the sarcolemma of muscle fibers. Precisely how dystrophin functions is far from clear. The presence of an array of isoforms of the C-terminal region of dystrophin suggests that dystrophin may have functions other than structural. In agreement, many potential phosphorylation sites are found in the C-terminal region of dystrophin, and the C-terminal region of dystrophin is phosphorylated both in vitro and in vivo by many protein kinases, including MAP kinase, p34cdc2 kinase, CaM kinase, and casein kinase, and is dephosphorylated by calcineurin. The C-terminal domain of dystrophin is also a substrate for hierarchical phosphorylation by casein kinase-2 and GSK-3. These observations, in accordance with the finding that the cysteine-rich region binds to Ca2+, Zn2+, and calmodulin, suggest an active involvement of dystrophin in transducing signals across muscle sarcolemma. Phosphorylation-dephosphorylation of the C-terminal region of dystrophin may play a role in regulating dystrophin-protein interactions and (or) transducing signal from the extracellular matrix via the dystrophin molecule to the cytoskeleton.
肌营养不良蛋白是导致杜氏和贝克型肌营养不良症的基因的蛋白质产物。该蛋白定位于肌膜的内表面，并与一组膜（糖）蛋白相关联。肌营养不良蛋白通过肌营养不良蛋白相关蛋白复合物将细胞骨架肌动蛋白与细胞外基质蛋白层粘连蛋白连接起来。这种结构组织暗示了肌营养不良蛋白在稳定肌纤维肌膜方面的作用。肌营养不良蛋白的确切功能尚不清楚。肌营养不良蛋白C末端区域存在一系列同工型，这表明肌营养不良蛋白可能具有结构以外的功能。与此一致的是，在肌营养不良蛋白的C末端区域发现了许多潜在的磷酸化位点，并且在体外和体内，肌营养不良蛋白的C末端区域都被许多蛋白激酶磷酸化，包括丝裂原活化蛋白激酶、p34cdc2激酶、钙调蛋白激酶和酪蛋白激酶，并且被钙调神经磷酸酶去磷酸化。肌营养不良蛋白的C末端结构域也是酪蛋白激酶-2和糖原合成酶激酶-3进行分级磷酸化的底物。这些观察结果，与富含半胱氨酸的区域与Ca2+、Zn2+和钙调蛋白结合的发现一致，表明肌营养不良蛋白积极参与跨肌肉肌膜的信号转导。肌营养不良蛋白C末端区域的磷酸化-去磷酸化可能在调节肌营养不良蛋白-蛋白质相互作用和（或）通过肌营养不良蛋白分子将细胞外基质的信号转导至细胞骨架中发挥作用。
