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 cells, we analyzed the changes in phosphorylation and cellular localization of these isoforms upon stimulation of prostate tumor cells with epidermal growth factor (EGF). EGF stimulation of prostate tumor cells resulted in transient increases in MHC-A and MHC-B phosphorylation and subcellular localization 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 our knowledge, this is the first report demonstrating that MHC phosphorylation might regulate its subcellular localization and that the EGF signal is transmitted to MHC-A and MHC-B via PKC. The correlation between MHC-B phosphorylation and localization in response to EGF stimulation might suggest that MHC-B is the myosin II isoform that is involved in chemotaxis.
Straussman
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Department of Biochemistry, Hadassah Medical School The Hebrew University, Jerusalem, Israel. ravid@md2.huji.ac.il
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Ravid
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D000409:Alanine / Q000235:genetics / Q000378:metabolism; D019943:Amino Acid Substitution / Q000235:genetics; D015153:Blotting, Western; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003001:Cloning, Molecular; D004789:Enzyme Activation / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D006801:Humans; D008297:Male; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D024462:Myosin Type II / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011467:Prostate / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D020033:Protein Isoforms; D004815:Epidermal Growth Factor; D011493:Protein Kinase C; D024462:Myosin Type II; D018995:Myosin Heavy Chains; D013755:Tetradecanoylphorbol Acetate; D000409:Alanine