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| DISRUPTION OF INTEGRIN FUNCTION AND INDUCTION OF TYROSINE PHOSPHORYLATION BY THE AUTONOMOUSLY EXPRESSED BETA(1) INTEGRIN CYTOPLASMIC DOMAIN |
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| Author(s): LUKASHEV ME, SHEPPARD D, PYTELA R |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 269 Issue: 28 Pages: 18311-18314 Published: JUL 15 1994 |
| Times Cited: 143 References: 26 |
| Abstract: The cytoplasmic domains of integrin beta subunits are essential for the function of integrins in cell adhesion and signaling. A chimera combining the transmembrane and cytoplasmic domains of the beta(1) integrin subunit with an irrelevant extracellular domain derived from L3T4 (murine CD4) was tested for its ability to interfere with integrin function. Expression of this construct in cultured human embryonic kidney cells under the control of the inducible metallothionein promoter resulted in cell rounding and detachment, and blocked cell adhesion mediated by the beta(1) and alpha(v) beta(5) integrins. Expression of the beta(1) chimera at basal levels interfered with the tyrosine phosphorylation of a 125-kDa protein induced by antibody-induced clustering of integrins. Induced expression of the chimera resulted in sustained tyrosine phosphorylation of this protein, which could be enhanced by clustering of the chimera but was insensitive to clustering of integrins. These results demonstrate that the autonomously expressed beta(1) integrin cytoplasmic domain can act as a trans-dominant inhibitor of integrin function, presumably via competitive interactions with cytoplasmic components that are required for integrin-mediated cell adhesion and tyrosine phosphorylation. |
| Document Type: Note |
| Language: English |
| Reprint Address: LUKASHEV, ME (reprint author), UNIV CALIF SAN FRANCISCO, CTR LUNG BIOL, DEPT MED, BOX 0854, SAN FRANCISCO, CA 94143 USA |
Addresses:
1. UNIV CALIF SAN FRANCISCO, DEPT PHARMACOL, SAN FRANCISCO, CA 94143 USA
2. UNIV CALIF SAN FRANCISCO, CARDIOVASC RES INST, SAN FRANCISCO, CA 94143 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: NW798 |
| ISSN: 0021-9258 |
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