AN ESSENTIAL ROLE OF PHOSPHATIDYLINOSITOL 3-KINASE IN MYOGENIC DIFFERENTIATION

The oncogene p3k, coding for a constitutively active form of phosphati dylinositol 3-kinase (PI 3-kinase; EC 2.7.1.137), strongly enhances my ogenic differentiation in cultures of chicken-embryo myoblasts. It inc reases the size of the myotubes and induces elevated levels of the mus cle-specific proteins MyoD, myosin heavy chain, creatine kinase, and d esmin. Inhibition of PI 3-kinase activity with LY294002 or with domina nt-negative mutants of PI 3-kinase interferes with myogenic differenti ation and with the induction of muscle-specific genes. PI3-kinase is t herefore an upstream mediator for the expression of the muscle-specifi c genes and is both necessary and rate-limiting for the process of myo genesis.