A Membrane-distal Segment of the Integrin αIIbCytoplasmic Domain Regulates Integrin Activation

Previous evidence suggests that interactions between integrin cytoplasmic domains regulate integrin activation. We have constructed and validated recombinant structural mimics of the heterodimeric αIIbβ3 cytoplasmic domain. The mimics elicited polyclonal antibodies that recognize a combinatorial epi...

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Published in:The Journal of biological chemistry 2001-06, Vol.276 (25), p.22514-22521
Main Authors: Ginsberg, Mark H., Yaspan, Brian, Forsyth, Jane, Ulmer, Tobias S., Campbell, Iain D., Slepak, Marina
Format: Article
Language:English
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Summary:Previous evidence suggests that interactions between integrin cytoplasmic domains regulate integrin activation. We have constructed and validated recombinant structural mimics of the heterodimeric αIIbβ3 cytoplasmic domain. The mimics elicited polyclonal antibodies that recognize a combinatorial epitope(s) formed in mixtures of the αIIband β3 cytoplasmic domains but not present in either isolated tail. This epitope(s) is present within intact αIIbβ3, indicating that interaction between the tails can occur in the native integrin. Furthermore, the combinatorial epitope(s) is also formed by introducing the activation-blocking β3(Y747A) mutation into the β3 tail. A membrane-distal heptapeptide sequence in the αIIb tail (997RPPLEED) is responsible for this effect on β3. Membrane-permeant palmitoylated peptides, containing this αIIb sequence, specifically blocked αIIbβ3 activation in platelets. Thus, this region of the αIIb tail causes the β3 tail to resemble that of β3(Y747A) and suppresses activation of the integrin.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M101915200