Control of the distribution of hemidesmosome components in cultured keratinocytes: Ca2+ and phorbol esters.
DJM-1 cells (a human squamous cell carcinoma cell line) grown in low Ca2+ medium did not form cell-cell junctions of desmosome-keratin intermediate filament (KIF). When they were shifted to normal (high) Ca2+ medium, rapid translocation of desmoplakins from the cytosol to the plasma membrane to form desmosomes and reorganization of 180 kd-hemidesmosome proteins were induced almost simultaneously. In correlation with these morphological responses, the Ca2+ shift caused a breakdown of inositol phospholipids, a formation of diacylglycerol (DAG) and inositol trisphosphate (IP3), protein kinase C (PKC) activation, and Ca2+ influx. 12-0-tetradecanoylphorbol-13-acetate (TPA)-treatment of low Ca(2+)-grown DJM-1 cells also caused desmosome formation in association with PKC activation. These TPA effects were cancelled with PKC inhibitors, 1-(5-isoquinolinylsulfomyl)-2-methylpiperazine (H7) and staurosporine. Treatment with other PKC-activating agents, phorbol-12,13-butyrate (PDBu) and diaoctanoylglycerol (DOG), also induced desmosome formation. TPA-treatment of normal Ca(2+)-grown cells collapsed the organized distribution of the 180 kd-hemidesmosome protein and appeared to detach this protein from the cell-matrix adhering sites. This effect was also inhibited by H7. These results suggest that PKC activation plays important roles in upregulation of cell-cell junctions and downregulation of cell-matrix junctions in association with differentiation of keratinocytes.
Kitajima
Y
Y
Department of Dermatology, Jichi Medical School, Tochigi, Japan.
Owaribe
K
K
Nishizawa
Y
Y
Yaoita
H
H
D002118:Calcium / Q000494:pharmacology*; D003896:Desmosomes / Q000502:physiology* / Q000648:ultrastructure; D004789:Enzyme Activation; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology; D015603:Keratinocytes / Q000378:metabolism / Q000648:ultrastructure*; D007633:Keratins / Q000502:physiology; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D010716:Phosphatidylinositols; D007633:Keratins; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium