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| Epidermal growth factor receptor relocalization and kinase activity are necessary for directional migration of keratinocytes in DC electric fields |
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| Author(s): Fang KS, Ionides E, Oster G, Nuccitelli R, Isseroff RR |
| Source: JOURNAL OF CELL SCIENCE Volume: 112 Issue: 12 Pages: 1967-1978 Published: JUN 1999 |
| Times Cited: 57 References: 121 |
| Abstract: Human keratinocytes migrate towards the negative pole in DC electric fields of physiological strength. This directional migration is promoted by epidermal growth factor (EGF). To investigate how EGF and its receptor (EGFR) regulate this directionality, we first examined the effect of protein tyrosine kinase inhibitors, including PD158780, a specific inhibitor for EGFR, on this response. At low concentrations, PD158780 inhibited keratinocyte migration directionality, but not the rate of migration; at higher concentrations, it reduced the migration rate as well. The less specific inhibitors, genistein, lavendustin A and tyrphostin B46, reduced the migration rate, but did not affect migration directionality, These data suggest that inhibition of EGFR kinase activity alone reduces directed motility, and inhibition of multiple tyrosine kinases, including EGFR, reduces the cell migration rate. EGFR redistribution also correlates with directional migration. EGFR concentrated on the cathodal face of the cell as early as 5 minutes after exposure to electric fields. PD158780 abolished EGFR localization to the cathodal face. These data suggest that EGFR kinase activity and redistribution in the plasma membrane are required for the directional migration of keratinocytes in DC electric fields. This study provides the first insights into the mechanisms of directed cell migration in electric fields. |
| Document Type: Review |
| Language: English |
| Reprint Address: Isseroff, RR (reprint author), Univ Calif Davis, Dept Dermatol, TB192,1 Shields Ave, Davis, CA 95616 USA |
Addresses:
1. Univ Calif Davis, Dept Dermatol, Davis, CA 95616 USA
2. Univ Calif Davis, Sect Mol & Cellular Biol, Davis, CA 95616 USA
3. Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA
4. Univ Calif Berkeley, Dept Mol & Cellular Biol, Berkeley, CA 94720 USA |
| Publisher: COMPANY OF BIOLOGISTS LTD, BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND |
| Subject Category: Cell Biology |
| IDS Number: 214TJ |
| ISSN: 0021-9533 |
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