Kim J M, Yoon M Y, Kim J, Kim S S, Kang I, Ha J, Kim S S
School of Natural Science, Hanyang University, Seoul, 133-791, Korea.
Arch Biochem Biophys. 1999 Jul 1;367(1):67-73. doi: 10.1006/abbi.1999.1232.
Phosphatidylinositol 3-kinase (PI3-kinase) is known to be a crucial regulator of muscle differentiation. However, its downstream pathway for this function is quite obscure. In this experiment we demonstrated the regulatory mechanism of the differentiation of H9c2 cardiomyoblasts, focusing on PI3-kinase, protein kinase B/Akt (PKB/Akt) and p42/44 mitogen-activated protein kinase (p42/44 MAPK). When H9c2 cells stably transfected with a constitutively active p110 (H9c2-p110*), a constitutively active PKB/Akt (H9c2-Akt), and an empty vector (H9c2-con) were induced to differentiate, H9c2-p110* cells differentiated fastest, followed by H9c2-Akt cells. H9c2-con cells differentiated at the slowest rate. Consistent with this result, LY294002 completely blocked differentiation of all these transfected cell lines, whereas PD098059 had no effect on their differentiation. When H9c2-p110* cells were transiently transfected with a dominant negative form of PKB/Akt, differentiation was not affected. Taken together, we concluded that PI3-kinase, but not p42/44 MAPK, regulates differentiation of H9c2 cardiomyoblasts mainly through the PKB/Akt-independent pathway.
磷脂酰肌醇3激酶（PI3激酶）是已知的肌肉分化关键调节因子。然而，其在该功能中的下游途径尚不清楚。在本实验中，我们重点研究PI3激酶、蛋白激酶B/Akt（PKB/Akt）和p42/44丝裂原活化蛋白激酶（p42/44 MAPK），证明了H9c2心肌成纤维细胞分化的调节机制。当稳定转染组成型活性p110（H9c2-p110*）、组成型活性PKB/Akt（H9c2-Akt）和空载体（H9c2-con）的H9c2细胞被诱导分化时，H9c2-p110细胞分化最快，其次是H9c2-Akt细胞。H9c2-con细胞分化速率最慢。与该结果一致，LY294002完全阻断了所有这些转染细胞系的分化，而PD098059对它们的分化没有影响。当用显性负性形式的PKB/Akt瞬时转染H9c2-p110细胞时，分化不受影响。综上所述，我们得出结论，PI3激酶而非p42/44 MAPK主要通过不依赖PKB/Akt的途径调节H9c2心肌成纤维细胞的分化。
