"Inside-out" signal transduction inhibited by isolated integrin cytoplasmic domains
The affinities of integrin alpha beta heterodimers for extracellular ligands are important regulators of cell adhesion. Intracellular signals provoke changes in the integrin extracellular domain resulting in "activation," as manifested by an increase in affinity. Interactions of integrin c...
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Veröffentlicht in: | The Journal of biological chemistry 1994-07, Vol.269 (28), p.18307-18310 |
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Sprache: | eng |
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Zusammenfassung: | The affinities of integrin alpha beta heterodimers for extracellular ligands are important regulators of cell adhesion. Intracellular
signals provoke changes in the integrin extracellular domain resulting in "activation," as manifested by an increase in affinity.
Interactions of integrin cytoplasmic domains with intracellular elements may mediate this "inside-out signaling." Here we
report that overexpression of chimeras of the cytoplasmic domain of integrin beta 3 or beta 1 subunits, joined to the extracellular
and transmembrane domains of the Tac subunit of the interleukin-2 receptor, reduced integrin affinity. In contrast, chimeras
containing the cytoplasmic domain of alpha 5 or alpha IIb or of beta 3 bearing a mutation that disrupts inside-out signaling
lacked inhibitory activity. These data suggest that limiting quantities of intracellular factors bind to integrin beta 3 and
beta 1 cytoplasmic domains to modulate ligand binding affinity. Structural mimics of these domains may provide a novel means
to alter cell adhesion. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/S0021-9258(17)32306-2 |