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© The Rockefeller University Press,
0021-9525/1999//1147 $5.00
The Journal of Cell Biology, Volume 146, Number 5,
, 1999 1147-1160
Original Article |
Protein Kinase C–Dependent Mobilization of the 
6β4 Integrin from Hemidesmosomes and Its Association with Actin-Rich Cell Protrusions Drive the Chemotactic Migration of Carcinoma Cells
amercuri{at}bidmc.harvard.edu
We explored the hypothesis that the chemotactic migration of carcinoma cells that assemble hemidesmosomes involves the activation of a signaling pathway that releases the
6β4 integrin from these stable adhesion complexes and promotes its association with F-actin in cell protrusions enabling it to function in migration. Squamous carcinoma-derived A431 cells were used because they express 6β4 and migrate in response to EGF stimulation. Using function-blocking antibodies, we show that the 6β4 integrin participates in EGF-stimulated chemotaxis and is required for lamellae formation on laminin-1. At concentrations of EGF that stimulate A431 chemotaxis (
1 ng/ml), the 6β4 integrin is mobilized from hemidesmosomes as evidenced by indirect immunofluorescence microscopy using mAbs specific for this integrin and hemidesmosomal components and its loss from a cytokeratin fraction obtained by detergent extraction. EGF stimulation also increased the formation of lamellipodia and membrane ruffles that contained 6β4 in association with F-actin. Importantly, we demonstrate that this mobilization of 6β4 from hemidesmosomes and its redistribution to cell protrusions occurs by a mechanism that involves activation of protein kinase C- and that it is associated with the phosphorylation of the β4 integrin subunit on serine residues. Thus, the chemotactic migration of A431 cells on laminin-1 requires not only the formation of F-actin–rich cell protrusions that mediate 6β4-dependent cell movement but also the disruption of 6β4-containing hemidesmosomes by protein kinase C.
Key Words: integrins • cell movement • PKC • hemidesmosomes • cytoskeleton
© 1999 The Rockefeller University Press
1.used in this paper: BPAG, bullous pemphigoid antigen; EGFR, EGF receptor; PKC, protein kinase C; PLC, phospholipase C; PI3K, phosphoinositide 3-OH kinase
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