The cytoplasmic domains of integrin β subunits are involved in bidirectional transmembrane signaling. We report that the cytoplasmic domain of the integrin β3 subunit undergoes limited proteolysis by calpain, an intracellular calcium-dependent protease. Calpain cleavage occurs during platelet aggregation induced by agonists such as thrombin. Five cleavage sites have been identified. Four of these sites (C-terminal to Thr741, Tyr747, Phe754, and Tyr759) are utilized in intact platelets and flank two NXXY motifs (Asn744-Pro-Leu-Tyr747 and Asn756-Ile-Thr-Tyr759). The fifth site (Ala735) is accessible to calpain after EDTA treatment of the αIIbβ3 heterodimer. The NXXY motif is critical to the bidirectional signaling functions of β3 integrins and their association with the cytoskeleton. Thus, calpain cleavage of the β3 cytoplasmic domain may provide a means to regulate integrin signaling functions.
Calpain Cleavage of the Cytoplasmic Domain of the Integrin β2 Subunit (*)
Xiaoping Du,T. Saido,S. Tsubuki,F. Indig,Michael J. Williams,M. Ginsberg
Published 1995 in Journal of Biological Chemistry
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- Publication year
1995
- Venue
Journal of Biological Chemistry
- Publication date
1995-11-03
- Fields of study
Biology, Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
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