Calpain cleavage of the cytoplasmic domain of the integrin beta 3 subunit

J Biol Chem. 1995 Nov 3;270(44):26146-51. doi: 10.1074/jbc.270.44.26146.

Abstract

The cytoplasmic domains of integrin beta subunits are involved in bidirectional transmembrane signaling. We report that the cytoplasmic domain of the integrin beta 3 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 alpha IIb beta 3 heterodimer. The NXXY motif is critical to the bidirectional signaling functions of beta 3 integrins and their association with the cytoskeleton. Thus, calpain cleavage of the beta 3 cytoplasmic domain may provide a means to regulate integrin signaling functions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD / isolation & purification
  • Antigens, CD / metabolism*
  • Blood Platelets / metabolism
  • Calpain / metabolism*
  • Cytoplasm
  • Humans
  • Integrin beta3
  • Molecular Sequence Data
  • Muscle, Skeletal / enzymology
  • Peptide Fragments / chemistry
  • Peptide Fragments / isolation & purification
  • Platelet Aggregation
  • Platelet Glycoprotein GPIIb-IIIa Complex / isolation & purification
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism*
  • Rabbits
  • Substrate Specificity
  • Thrombin / pharmacology

Substances

  • Antigens, CD
  • Integrin beta3
  • Peptide Fragments
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Thrombin
  • Calpain