Phorbol ester-induced migration of HepG2 cells is accompanied by intensive stress fibre formation, enhanced integrin expression and transient down-regulation of p21-activated kinase 1.
Previously, we observed that phorbol ester induced more intensive scattering of HepG2 human hepatoma cells than hepatocyte growth factor (HGF). Regulatory components accounting for this intensive migration were studied. Phorbol ester-activated protein kinase C induced the early appearance of a great number of actin stress fibres. Whereas in response to HGF, the activation of phosphatidylinositol 3-kinase initiates the rearrangements of the actin cytoskeleton, in phorbol ester-treated cells, the activation of this enzyme was not required to the actin polymerisation. Activation of Erk1/Erk2 MAP kinases that was essential to the migration had a key role in enhancing the adherence of cells to the extracellular matrix via the increased expression of integrins alpha2, alpha6 and beta1. Protein kinase C stimulated the activation of p21-activated kinase (PAK), as well. However, it also stimulated the selective and transient down-regulation of PAK1, which coincided with the formation of stress fibres.
Gujdár
Annamária
A
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University of Medicine, PO Box 260, 1444 Budapest, Hungary.
Sipeki
Szabolcs
S
Bander
Erzsébet
E
Buday
László
L
Faragó
Anna
A
D008841:Actin Cytoskeleton / Q000187:drug effects / Q000201:enzymology; D002273:Carcinogens / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D002465:Cell Movement / Q000187:drug effects*; D015536:Down-Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D039421:Integrin alpha2 / Q000378:metabolism; D039503:Integrin alpha6 / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D008113:Liver Neoplasms; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D022502:Stress Fibers / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D054462:p21-Activated Kinases
D002273:Carcinogens; D039421:Integrin alpha2; D039503:Integrin alpha6; D019012:Integrin beta1; C515903:PAK1 protein, human; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D013755:Tetradecanoylphorbol Acetate