Phosphatidylinositol 3-kinase regulates differentiation of H9c2 cardiomyoblasts mainly through the protein kinase B/Akt-independent pathway

Phosphatidylinositol 3-kinase (PI3-kinase) is known to be a crucial regulat or of muscle differentiation. However, its downstream pathway for this func tion is quite obscure. In this experiment we demonstrated the regulatory me chanism of the differentiation of H9c2 cardiomyoblasts, focusing on PI3-kin ase, protein kinase B/Akt (PKB/Akt) and p42/44 mitogen-activated protein ki nase (p42/44 MAPK). When H9c2 cells stably transfected with a constitutivel y active p110 (H9c2-p110*), a constitutively active PKB/Akt (H9ca-Akt), and an empty vector (H9c2-con) were induced to differentiate, H9c2-p110* cells differentiated fastest, followed by H9c2-Akt cells. H9c2-con cells differe ntiated at the slowest rate. Consistent with this result, LY294002 complete ly blocked differentiation of all these transfected cell lines, whereas PD0 98059 had no effect on their differentiation. When H9c2-p110* cells were tr ansiently transfected with a dominant negative form of PKB/Akt, differentia tion was not affected. Taken together, we concluded that PI3-kinase, but no t p42/44 MAPK, regulates differentiation of H9c2 cardiomyoblasts mainly thr ough the PKB/Akt-independent pathway. (C) 1999 Academic Press.