| | |  | | | | Record from Web of Science® | | | | | | |
| Complementation of dominant suppression implicates CD98 in integrin activation |
|
|
| Author(s): Fenczik CA, Sethi T, Ramos JW, Hughes PE, Ginsberg MH |
| Source: NATURE Volume: 390 Issue: 6655 Pages: 81-85 Published: NOV 6 1997 |
| Times Cited: 169 References: 25 |
| Abstract: The integrin family of adhesion receptors are involved in cell growth, migration and tumour metastasis(1). Integrins are heterodimeric proteins composed of an alpha and a beta subunit, each with a large extracellular, a single transmembrane, and a short cytoplasmic domain. The dynamic regulation of integrin affinity for ligands in response to cellular signals is central to integrin function(2). This process is energy dependent and is mediated through integrin cytoplasmic domains(3). However, the cellular machinery regulating integrin affinity remains poorly understood. Here we describe a genetic strategy to disentangle integrin signalling pathways. Dominant suppression occurs when overexpression of isolated integrin beta(1) cytoplasmic domains blocks integrin activation. Proteins involved in integrin signalling were identified by their capacity to complement dominant suppression in an expression cloning scheme. CD98, an early T-cell activation antigen that associates with functional integrins(4), was found to regulate integrin activation. Furthermore, antibody-mediated crosslinking of CD98 stimulated beta(1) integrin-dependent cell adhesion. These data indicate that CD98 is involved in regulating integrin affinity, and validate an unbiased genetic approach to analysing integrin signalling pathways. |
| Document Type: Article |
| Language: English |
Addresses:
1. Scripps Res Inst, DEPT VASC BIOL, LA JOLLA, CA 92037 USA
2. UNIV EDINBURGH, SCH MED, DEPT RESP MED, EDINBURGH EH8 9AG, MIDLOTHIAN SCOTLAND |
| Publisher: MACMILLAN MAGAZINES LTD, PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: YE477 |
| ISSN: 0028-0836 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |