Myosin II heavy chain isoforms are phosphorylated in an EGF-dependent manner: involvement of protein kinase C

To explore the involvement and regulation of the nonmuscle myosin II heavy chains isoforms, MHC-A and MHC-B in the chemotaxis of metastatic tumor cell s, we analyzed the changes in phosphorylation and cellular localization of these isoforms upon stimulation of prostate tumor cells with epidermal grow th factor (EGF). EGF stimulation of prostate tumor cells resulted in transi ent increases in MHC-A and MHC-B phosphorylation and subcellular localizati on with quite different kinetics. Furthermore, the kinetics of subcellular localization correlated with the in vivo kinetics of MHC-B phosphorylation but not of MHC-A phosphorylation, suggesting different modes of regulation for these myosin II isoforms. We further showed that protein kinase C (PKC) is involved in the EGF-dependent phosphorylation of MHC-A and MHC-B. To ou r knowledge, this is the first report demonstrating that MHC phosphorylatio n might regulate its subcellular localization and that the EGF signal is tr ansmitted to MHC-A and MHC-B via PKC. The correlation between MHC-B phospho rylation and localization in response to EGF stimulation might suggest that MHC-B is the myosin II isoform that is involved in chemotaxis.