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| Regulation of focal adhesion kinase by a novel protein inhibitor FIP200 |
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| Author(s): Abbi S, Ueda H, Zheng CH, Cooper LA, Zhao JH, Christopher R, Guan JL |
| Source: MOLECULAR BIOLOGY OF THE CELL Volume: 13 Issue: 9 Pages: 3178-3191 Published: SEP 2002 |
| Times Cited: 31 References: 56 |
| Abstract: Focal adhesion kinase (FAK) is a major mediator of integrin signaling pathways. The mechanisms of regulation of FAK activity and its associated cellular functions are not very well understood. Here, we present data suggesting that a novel protein FIP200 functions as an inhibitor for FAK. We show the association of endogenous FIP200 with FAK, which is decreased upon integrin-mediated cell adhesion concomitant with FAK activation. In vitro- and in vivo-binding studies indicate that FIP200 interacts with FAK through multiple domains directly. FIP200 bound to the kinase domain of FAK inhibited its kinase activity in vitro and its autophosphorylation in vivo. Overexpression of FIP200 or its sements inhibited cell spreading, cell migration, and cell cycle progression, which correlated with their inhibition of FAK activity in vivo. The inhibition of these cellular functions by FIP200 could be rescued by coexpression of FAK. Last, we show that disruption of the functional interaction between endogenous FIP200 with FAK leads to increased FAK phosphorylation and partial restoration of cell cycle progression in cells plated on poly-L-lysine, providing further support for FIP200 as a negative regulator of FAK. Together, these results identify FIP200 as a novel protein inhibitor for FAK. |
| Document Type: Article |
| Language: English |
| Reprint Address: Guan, JL (reprint author), Cornell Univ, Coll Vet Med, Dept Mol Med, Ithaca, NY 14853 USA |
Addresses:
1. Cornell Univ, Coll Vet Med, Dept Mol Med, Ithaca, NY 14853 USA |
| Publisher: AMER SOC CELL BIOLOGY, 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA |
| Subject Category: Cell Biology |
| IDS Number: 598GU |
| ISSN: 1059-1524 |
| DOI: 10.1091/mbc.E02-05-0295 |
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