Recognition of the N-terminal Modules of Thrombospondin-1 and Thrombospondin-2 by α6β1 Integrin*

By M. J. Calzada, J. M. Sipes, H. Krutzsch, P. Yurchenco, D. Annis, D. Mosher, D. Roberts. Journal of Biological Chemistry, 2003

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In addition to its recognition by α3β1 and α4β1 integrins, the N-terminal pentraxin module of thrombospondin-1 is a ligand for α6β1 integrin. α6β1 integrin mediates adhesion of human microvascular endothelial and HT-1080 fibrosarcoma cells to immobilized thrombospondin-1 and recombinant N-terminal regions of thrombospondin-1 and thrombospondin-2. α6β1 also mediates chemotaxis of microvascular cells to thrombospondin-1 and thrombospondin-2. Using synthetic peptides, LALERKDHSG was identified as an α6β1-binding sequence in thrombospondin-1. This peptide inhibited α6β1-dependent cell adhesion to thrombospondin-1, thrombospondin-2, and the E8 fragment of murine laminin-1. The Glu residue in this peptide was required for activity, and the corresponding residue (Glu90) in the N-terminal module of thrombospondin-1 was required for its recognition by α6β1, but not by α4β1. α6β1 was also expressed in human umbilical vein endothelial cells; but in these cells, only certain agonists could activate the integrin to recognize thrombospondins. Selective activation of α6β1 integrin in microvascular endothelial cells by the anti-β1 antibody TS2/16 therefore accounts for their adhesion responses to thrombospondins and explains the distinct functions of α4β1 and α6β1 integrins as thrombospondin receptors in microvascular and large vessel endothelial cells.

Subfields: Cancer Research, Hematology, Immunology and Allergy

View Paper: https://www.semanticscholar.org/paper/61a843e1471c856dd29fd012fe7eeab88fd19e3d

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Citations in the corpus

The thrombospondins. (2011, background): “Binding sites for integrins a3b1 and a6b1 have been mapped to the LG-NTD, yet the physiological significance of these remains uncertain because the identified motifs are not fully surfaceexposed in the crystal structure (Krutzsch et al. 1999; Calzada et al. 2003; Tan et al. 2006).”