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The ligand binding affinities of the integrins are regulated
through their cytoplasmic domains. To identify specific residues that
are involved in this process, we have generated mutants in the
Volume 270,
Number 15,
Issue of April 14, pp. 8553-8558, 1995
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Subunit Cytoplasmic Domain
and 
tails and coexpressed them in
Chinese hamster ovary cells with constitutively active 
subunits.
These subunits are chimera of extracellular and transmembrane
joined to the cytoplasmic domains of
, , or
and confer
an energy-dependent high affinity state when expressed in Chinese
hamster ovary cells. The affinity state of these transfectants was
determined by analyzing the binding of PAC1, an antibody that
specifically recognizes the activated form of the reporter group,
extracellualar
. We have identified
point mutants in several areas of the tails, which result in a
reduced ability to bind ligand. Complete abolition of PAC1 binding was
obtained with mutants in an NP XY motif found in many integrin
subunits and implicated in the internalization of other cell
surface receptors. Similar effects on PAC1 binding were observed
whether coexpression was with chimera containing
, , or
cytoplasmic sequences. These studies identify a novel role for
the NP XY motif in the regulation of integrin binding affinity.
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