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Recognition of the N-terminal modules of thrombospondin-1 and thrombospondin-2 by alpha6beta1 integrin.
Calzada, Maria J; Sipes, John M; Krutzsch, Henry C; Yurchenco, Peter D; Annis, Douglas S; Mosher, Deane F; Roberts, David D.
Affiliation
  • Calzada MJ; Laboratory of Pathology, NCI, National Institutes of Health, Bethesda, Maryland 20892-1500, USA.
J Biol Chem ; 278(42): 40679-87, 2003 Oct 17.
Article in En | MEDLINE | ID: mdl-12909644
In addition to its recognition by alpha3beta1 and alpha4beta1 integrins, the N-terminal pentraxin module of thrombospondin-1 is a ligand for alpha6beta1 integrin. alpha6beta1 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. alpha6beta1 also mediates chemotaxis of microvascular cells to thrombospondin-1 and thrombospondin-2. Using synthetic peptides, LALERKDHSG was identified as an alpha6beta1-binding sequence in thrombospondin-1. This peptide inhibited alpha6beta1-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 alpha6beta1, but not by alpha4beta1. alpha6beta1 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 alpha6beta1 integrin in microvascular endothelial cells by the anti-beta1 antibody TS2/16 therefore accounts for their adhesion responses to thrombospondins and explains the distinct functions of alpha4beta1 and alpha6beta1 integrins as thrombospondin receptors in microvascular and large vessel endothelial cells.
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Collection: 01-internacional Database: MEDLINE Main subject: Thrombospondins / Thrombospondin 1 / Integrin alpha6beta1 Limits: Animals / Humans Language: En Journal: J Biol Chem Year: 2003 Type: Article Affiliation country: United States
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Collection: 01-internacional Database: MEDLINE Main subject: Thrombospondins / Thrombospondin 1 / Integrin alpha6beta1 Limits: Animals / Humans Language: En Journal: J Biol Chem Year: 2003 Type: Article Affiliation country: United States