Calcium Integrin Binding Protein Associates with Integrins α V β 3 and α IIb β 3 Independent of β 3 Activation Motifs

• Published in: CellBio (Irvine, Calif. Print) Vol. 1; no. 2; p. 30
• Main Authors: Yamodo, Innocent H, Blystone, Scott D
• Format: Journal Article
• Language: English
• Published: United States 18.12.2012
• Subjects: Signaling; Cytoskeleton; Activation; Integrin; Hematopoietic; Leukocyte
• ISSN: 2325-7776
• DOI: 10.4236/cellbio.2012.12004

The Calcium Integrin Binding protein (CIB) has been identified as interacting specifically with the cytoplasmic tail of the integrin α domain to induce receptor activation and integrin α β mediated cell adhesion to extracellular proteins. In K562 cells stably expressing mutated integrin α β , or chimeric α β carrying α cytoplasmic tail, we report that the interaction of CIB with β integrins is not α β specific but binds α as well as α cytoplasmic tail domains. A double mutation of two proline residues to alanine residues in the α cytoplasmic domain, previously shown to disturb its conformation, inhibits chimeric α /α β -CIB interaction. This demonstrates that α cytoplasmic domain loop-like conformation is required for interaction with CIB. Moreover, mutations of β cytoplasmic domain residues Tyr-747 and/or Tyr-759 to phenylalanine residues (Y747F, Y759F, and Y747,759F) as well as residues Ser-752 to proline or alanine (S752P and S752A), do not affect the α β or α β interaction with CIB. Since tyrosine residues Tyr-747 and/or Tyr-759 are the sites of tyrosine phosphorylation of β subunit, these results suggest that the β integrin-CIB interaction occurs through a β -phosphorylation independent mechanism. Likewise, ablation of conformation-dependent affinity change in β Ser752Pro mutation had no affect on CIB-β interaction. In summary, our results demonstrate that the α -subunit integrin and CIB interaction is non-exclusive and requires the loop-like α -cytoplasmic domain conformation. An interaction of CIB with α -containing integrins provides an additional role for this molecule in keeping with its expression outside of platelets.