INTEGRINS
PKC
Controls Intracellular Movement
Integrins mediate cell adhesion and signaling events. The turnover and movement of adhesion sites is critical for cell migration. Ivaska et al. examined how protein kinase C 
(PKC) influenced cell migration and B1 integrins in mouse embryonic fibroblasts deficient in PKC (PKCKO). Cell lines in which PCK had been reintroduced (PKCRE) exhibited more migratory behavior and more peripheral focal adhesions than did PKCKO cells. The increased migration toward fibronectin required the kinase activity of PCK. When PKC activity was inhibited in the PKCRE cells by bis-indolylmaleimide I (BIM I), ß1 integrin from the plasma membrane, PKC, and a tetraspanin protein CD81 accumulated in intracellular vesicles, suggesting that PKC regulates a step in integrin endocytosis and intracellular trafficking. Cells from the PKCKO did not show this same redistribution of integrins; however, after transfection of the kinase-inactive mutant of PKC vesicular localization was detected. Thus, absence of PCK may not be equivalent to inhibition of PKC. In vitro, release of PKC from vesicles isolated after BIM I treatment required energy and PKC kinase activity, suggesting that PKC activity regulates recycling from this compartment.
J. Ivaska, R. D. H. Whelan, R. Watson, P. J. Parker, PKC controls the traffic of ß1 integrins in motile cells. EMBO J. 21, 3608-3619 (2002).
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